rs76661336

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.*113C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0583 in 840,902 control chromosomes in the GnomAD database, including 1,658 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 241 hom., cov: 32)

Exomes 𝑓: 0.060 ( 1417 hom. )

Consequence

SLX4
NM_032444.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0920

Publications

6 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:

ENSG00000261938 (HGNC:):

ENSG00000261938 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=-0.81).

BP6

Variant 16-3582229-G-A is Benign according to our data. Variant chr16-3582229-G-A is described in ClinVar as Benign. ClinVar VariationId is 319141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
SLX4	NM_032444.4 link	c.*113C>T	3_prime_UTR_variant	Exon 15 of 15	ENST00000294008.4	NP_115820.2
SLX4	XM_024450471.2 link	c.*113C>T	3_prime_UTR_variant	Exon 15 of 15		XP_024306239.1
SLX4	XM_011522715.4 link	c.*113C>T	3_prime_UTR_variant	Exon 15 of 15		XP_011521017.1
SLX4	XM_047434801.1 link	c.*113C>T	3_prime_UTR_variant	Exon 11 of 11		XP_047290757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLX4	ENST00000294008.4 link	c.*113C>T		3_prime_UTR_variant	Exon 15 of 15	5	NM_032444.4	ENSP00000294008.3
ENSG00000261938	ENST00000573982.1 link	n.198+851G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.0504

AC:

7572

AN:

150098

Hom.:

241

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0120

Gnomad AMI

AF:

0.0910

Gnomad AMR

AF:

0.0690

Gnomad ASJ

AF:

0.0188

Gnomad EAS

AF:

0.0372

Gnomad SAS

AF:

0.0545

Gnomad FIN

AF:

0.0910

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.0655

Gnomad OTH

AF:

0.0488

GnomAD4 exome

AF:

0.0600

AC:

41466

AN:

690698

Hom.:

1417

Cov.:

AF XY:

0.0595

AC XY:

21300

AN XY:

358018

show subpopulations

African (AFR)

AF:

0.0100

AC:

186

AN:

18548

American (AMR)

AF:

0.0648

AC:

2091

AN:

32290

Ashkenazi Jewish (ASJ)

AF:

0.0187

AC:

334

AN:

17820

East Asian (EAS)

AF:

0.0318

AC:

1038

AN:

32622

South Asian (SAS)

AF:

0.0532

AC:

3066

AN:

57664

European-Finnish (FIN)

AF:

0.0813

AC:

2561

AN:

31488

Middle Eastern (MID)

AF:

0.0286

AC:

AN:

2588

European-Non Finnish (NFE)

AF:

0.0654

AC:

30274

AN:

463050

Other (OTH)

AF:

0.0532

AC:

1842

AN:

34628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

2186

4372

6559

8745

10931

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

634

1268

1902

2536

3170

<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:

0.0504

AC:

7568

AN:

150204

Hom.:

241

Cov.:

AF XY:

0.0519

AC XY:

3801

AN XY:

73298

show subpopulations

African (AFR)

AF:

0.0120

AC:

491

AN:

40982

American (AMR)

AF:

0.0687

AC:

1040

AN:

15144

Ashkenazi Jewish (ASJ)

AF:

0.0188

AC:

AN:

3450

East Asian (EAS)

AF:

0.0371

AC:

186

AN:

5018

South Asian (SAS)

AF:

0.0554

AC:

261

AN:

4710

European-Finnish (FIN)

AF:

0.0910

AC:

913

AN:

10036

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0655

AC:

4426

AN:

67594

Other (OTH)

AF:

0.0479

AC:

100

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

353

705

1058

1410

1763

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<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:

0.0598

Hom.:

Bravo

AF:

0.0465

Asia WGS

AF:

0.0510

AC:

179

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

not specified

Benign:1

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. -

Fanconi anemia complementation group P

Benign:1

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.9

(source)

DANN

Benign

0.73

PhyloP100

0.092

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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