16-3589138-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032444.4(SLX4):c.4500T>C(p.Asn1500Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 1,613,870 control chromosomes in the GnomAD database, including 256,101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 33045 hom., cov: 31)

Exomes 𝑓: 0.54 ( 223056 hom. )

Consequence

SLX4
NM_032444.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.753

Publications

37 publications found

Variant links:

Genes affected

SLX4 (HGNC:23845): (SLX4 structure-specific endonuclease subunit) This gene encodes a protein that functions as an assembly component of multiple structure-specific endonucleases. These endonuclease complexes are required for repair of specific types of DNA lesions and critical for cellular responses to replication fork failure. Mutations in this gene were found in patients with Fanconi anemia. [provided by RefSeq, Sep 2016]

SLX4 Gene-Disease associations (from GenCC):

Fanconi anemia complementation group P
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
Fanconi anemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
familial ovarian cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
hereditary breast carcinoma
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

SLX4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 16-3589138-A-G is Benign according to our data. Variant chr16-3589138-A-G is described in ClinVar as Benign. ClinVar VariationId is 262053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.753 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLX4	NM_032444.4 link	c.4500T>C	p.Asn1500Asn	synonymous_variant	Exon 12 of 15	ENST00000294008.4	NP_115820.2	Q8IY92-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLX4	ENST00000294008.4 link	c.4500T>C	p.Asn1500Asn	synonymous_variant	Exon 12 of 15	5	NM_032444.4	ENSP00000294008.3		Q8IY92-1

Frequencies

GnomAD3 genomes

AF:

0.638

AC:

96966

AN:

151922

Hom.:

32978

Cov.:

show subpopulations

Gnomad AFR

AF:

0.875

Gnomad AMI

AF:

0.542

Gnomad AMR

AF:

0.619

Gnomad ASJ

AF:

0.488

Gnomad EAS

AF:

0.716

Gnomad SAS

AF:

0.774

Gnomad FIN

AF:

0.515

Gnomad MID

AF:

0.621

Gnomad NFE

AF:

0.512

Gnomad OTH

AF:

0.611

GnomAD2 exomes

AF:

0.604

AC:

151712

AN:

251234

AF XY:

0.602

show subpopulations

Gnomad AFR exome

AF:

0.878

Gnomad AMR exome

AF:

0.669

Gnomad ASJ exome

AF:

0.487

Gnomad EAS exome

AF:

0.720

Gnomad FIN exome

AF:

0.515

Gnomad NFE exome

AF:

0.513

Gnomad OTH exome

AF:

0.559

GnomAD4 exome

AF:

0.544

AC:

795369

AN:

1461830

Hom.:

223056

Cov.:

AF XY:

0.549

AC XY:

399049

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.892

AC:

29870

AN:

33480

American (AMR)

AF:

0.657

AC:

29363

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.482

AC:

12600

AN:

26136

East Asian (EAS)

AF:

0.738

AC:

29280

AN:

39700

South Asian (SAS)

AF:

0.758

AC:

65422

AN:

86258

European-Finnish (FIN)

AF:

0.517

AC:

27614

AN:

53372

Middle Eastern (MID)

AF:

0.561

AC:

3237

AN:

5766

European-Non Finnish (NFE)

AF:

0.507

AC:

564179

AN:

1111998

Other (OTH)

AF:

0.560

AC:

33804

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

24101

48202

72304

96405

120506

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16560

33120

49680

66240

82800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.639

AC:

97099

AN:

152040

Hom.:

33045

Cov.:

AF XY:

0.642

AC XY:

47715

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.875

AC:

36318

AN:

41512

American (AMR)

AF:

0.619

AC:

9466

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.488

AC:

1692

AN:

3466

East Asian (EAS)

AF:

0.716

AC:

3696

AN:

5162

South Asian (SAS)

AF:

0.774

AC:

3733

AN:

4826

European-Finnish (FIN)

AF:

0.515

AC:

5438

AN:

10558

Middle Eastern (MID)

AF:

0.620

AC:

181

AN:

292

European-Non Finnish (NFE)

AF:

0.512

AC:

34782

AN:

67922

Other (OTH)

AF:

0.616

AC:

1301

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1592

3184

4777

6369

7961

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

774

1548

2322

3096

3870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.552

Hom.:

108453

Bravo

AF:

0.654

Asia WGS

AF:

0.759

AC:

2640

AN:

3478

EpiCase

AF:

0.513

EpiControl

AF:

0.517

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group P

Benign:4

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Aug 31, 2012

Leiden Open Variation Database

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:curation

Curator: Arleen D. Auerbach. Submitter to LOVD: Janine Bakker. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 14, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Fanconi anemia

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.5

(source)

DANN

Benign

0.35

PhyloP100

0.75

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over