rs3810813

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032444.4(SLX4):c.3812C>T(p.Ser1271Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0597 in 1,613,372 control chromosomes in the GnomAD database, including 3,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 280 hom., cov: 32)

Exomes 𝑓: 0.061 ( 3310 hom. )

Consequence

SLX4
NM_032444.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.04

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015541315).

BP6

Variant 16-3589826-G-A is Benign according to our data. Variant chr16-3589826-G-A is described in ClinVar as [Benign]. Clinvar id is 262050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-3589826-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLX4	NM_032444.4 link	c.3812C>T	p.Ser1271Phe	missense_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.3812C>T	p.Ser1271Phe	missense_variant	Exon 12 of 15	5	NM_032444.4	ENSP00000294008.3		Q8IY92-1

Frequencies

GnomAD3 genomes

AF:

0.0498

AC:

7569

AN:

152140

Hom.:

276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0110

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0573

Gnomad ASJ

AF:

0.0317

Gnomad EAS

AF:

0.177

Gnomad SAS

AF:

0.0684

Gnomad FIN

AF:

0.0704

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0586

Gnomad OTH

AF:

0.0479

GnomAD3 exomes

AF:

0.0662

AC:

16583

AN:

250642

Hom.:

762

AF XY:

0.0659

AC XY:

8930

AN XY:

135574

show subpopulations

Gnomad AFR exome

AF:

0.00981

Gnomad AMR exome

AF:

0.0801

Gnomad ASJ exome

AF:

0.0355

Gnomad EAS exome

AF:

0.185

Gnomad SAS exome

AF:

0.0663

Gnomad FIN exome

AF:

0.0659

Gnomad NFE exome

AF:

0.0540

Gnomad OTH exome

AF:

0.0576

GnomAD4 exome

AF:

0.0607

AC:

88747

AN:

1461114

Hom.:

3310

Cov.:

AF XY:

0.0611

AC XY:

44390

AN XY:

726896

show subpopulations

Gnomad4 AFR exome

AF:

0.00860

Gnomad4 AMR exome

AF:

0.0761

Gnomad4 ASJ exome

AF:

0.0354

Gnomad4 EAS exome

AF:

0.198

Gnomad4 SAS exome

AF:

0.0653

Gnomad4 FIN exome

AF:

0.0647

Gnomad4 NFE exome

AF:

0.0569

Gnomad4 OTH exome

AF:

0.0618

GnomAD4 genome

AF:

0.0498

AC:

7577

AN:

152258

Hom.:

280

Cov.:

AF XY:

0.0510

AC XY:

3797

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0110

Gnomad4 AMR

AF:

0.0579

Gnomad4 ASJ

AF:

0.0317

Gnomad4 EAS

AF:

0.177

Gnomad4 SAS

AF:

0.0680

Gnomad4 FIN

AF:

0.0704

Gnomad4 NFE

AF:

0.0586

Gnomad4 OTH

AF:

0.0498

Alfa

AF:

0.0582

Hom.:

669

Bravo

AF:

0.0491

TwinsUK

AF:

0.0620

AC:

230

ALSPAC

AF:

0.0597

AC:

230

ESP6500AA

AF:

0.0132

AC:

ESP6500EA

AF:

0.0545

AC:

469

ExAC

AF:

0.0641

AC:

7783

Asia WGS

AF:

0.118

AC:

408

AN:

3478

EpiCase

AF:

0.0585

EpiControl

AF:

0.0551

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

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. -

Oct 30, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 24, 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

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.42

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.11

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.16

MPC

0.37

ClinPred

0.013

GERP RS

5.1

Varity_R

0.27

gMVP

0.42

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over