16-3597786-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032444.4(SLX4):c.1366+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0681 in 1,613,988 control chromosomes in the GnomAD database, including 4,100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.084 ( 603 hom., cov: 32)

Exomes 𝑓: 0.066 ( 3497 hom. )

Consequence

SLX4
NM_032444.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0620

Publications

9 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 16-3597786-A-G is Benign according to our data. Variant chr16-3597786-A-G is described in ClinVar as Benign. ClinVar VariationId is 262034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLX4	NM_032444.4 link	c.1366+11T>C		intron_variant	Intron 6 of 14	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.1366+11T>C		intron_variant	Intron 6 of 14	5	NM_032444.4	ENSP00000294008.3		Q8IY92-1
SLX4	ENST00000466154.5 link	n.2587+11T>C		intron_variant	Intron 4 of 6	1

Frequencies

GnomAD3 genomes

AF:

0.0840

AC:

12775

AN:

152062

Hom.:

600

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.0833

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.0364

Gnomad SAS

AF:

0.0572

Gnomad FIN

AF:

0.0869

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0675

Gnomad OTH

AF:

0.0766

GnomAD2 exomes

AF:

0.0685

AC:

17147

AN:

250472

AF XY:

0.0657

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.0782

Gnomad ASJ exome

AF:

0.0207

Gnomad EAS exome

AF:

0.0350

Gnomad FIN exome

AF:

0.0880

Gnomad NFE exome

AF:

0.0674

Gnomad OTH exome

AF:

0.0572

GnomAD4 exome

AF:

0.0665

AC:

97141

AN:

1461808

Hom.:

3497

Cov.:

AF XY:

0.0656

AC XY:

47700

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.124

AC:

4162

AN:

33480

American (AMR)

AF:

0.0754

AC:

3372

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0202

AC:

527

AN:

26134

East Asian (EAS)

AF:

0.0315

AC:

1252

AN:

39700

South Asian (SAS)

AF:

0.0569

AC:

4905

AN:

86252

European-Finnish (FIN)

AF:

0.0832

AC:

4439

AN:

53380

Middle Eastern (MID)

AF:

0.0452

AC:

261

AN:

5768

European-Non Finnish (NFE)

AF:

0.0667

AC:

74212

AN:

1111980

Other (OTH)

AF:

0.0664

AC:

4011

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

5863

11725

17588

23450

29313

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2746

5492

8238

10984

13730

<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:

0.0841

AC:

12795

AN:

152180

Hom.:

603

Cov.:

AF XY:

0.0844

AC XY:

6278

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.126

AC:

5226

AN:

41494

American (AMR)

AF:

0.0830

AC:

1269

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0196

AC:

AN:

3472

East Asian (EAS)

AF:

0.0363

AC:

188

AN:

5174

South Asian (SAS)

AF:

0.0578

AC:

279

AN:

4824

European-Finnish (FIN)

AF:

0.0869

AC:

922

AN:

10604

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0675

AC:

4592

AN:

68006

Other (OTH)

AF:

0.0758

AC:

160

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

613

1226

1838

2451

3064

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

276

414

552

690

<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:

0.0723

Hom.:

Bravo

AF:

0.0862

Asia WGS

AF:

0.0590

AC:

208

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group P

Benign:3

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

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

Feb 24, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

-0.92

CADD

Benign

7.4

(source)

DANN

Benign

0.29

PhyloP100

0.062

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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