rs78637028

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_032444.4(SLX4):c.2855C>T(p.Ala952Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0602 in 1,613,928 control chromosomes in the GnomAD database, including 3,253 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A952M) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.050 ( 238 hom., cov: 33)

Exomes 𝑓: 0.061 ( 3015 hom. )

Consequence

SLX4
NM_032444.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.432

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=0.0017929375).

BP6

Variant 16-3590783-G-A is Benign according to our data. Variant chr16-3590783-G-A is described in ClinVar as [Benign]. Clinvar id is 262045.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLX4	NM_032444.4 link	c.2855C>T	p.Ala952Val	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.2855C>T	p.Ala952Val	missense_variant	Exon 12 of 15	5	NM_032444.4	ENSP00000294008.3		Q8IY92-1

Frequencies

GnomAD3 genomes

AF:

0.0498

AC:

7578

AN:

152150

Hom.:

238

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0118

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.0691

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.0362

Gnomad SAS

AF:

0.0526

Gnomad FIN

AF:

0.0858

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0651

Gnomad OTH

AF:

0.0483

GnomAD3 exomes

AF:

0.0582

AC:

14609

AN:

251138

Hom.:

516

AF XY:

0.0578

AC XY:

7847

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.0116

Gnomad AMR exome

AF:

0.0690

Gnomad ASJ exome

AF:

0.0189

Gnomad EAS exome

AF:

0.0355

Gnomad SAS exome

AF:

0.0520

Gnomad FIN exome

AF:

0.0881

Gnomad NFE exome

AF:

0.0651

Gnomad OTH exome

AF:

0.0502

GnomAD4 exome

AF:

0.0613

AC:

89633

AN:

1461660

Hom.:

3015

Cov.:

AF XY:

0.0609

AC XY:

44248

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.00914

Gnomad4 AMR exome

AF:

0.0651

Gnomad4 ASJ exome

AF:

0.0189

Gnomad4 EAS exome

AF:

0.0317

Gnomad4 SAS exome

AF:

0.0531

Gnomad4 FIN exome

AF:

0.0829

Gnomad4 NFE exome

AF:

0.0649

Gnomad4 OTH exome

AF:

0.0552

GnomAD4 genome

AF:

0.0497

AC:

7575

AN:

152268

Hom.:

238

Cov.:

AF XY:

0.0513

AC XY:

3817

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0118

Gnomad4 AMR

AF:

0.0688

Gnomad4 ASJ

AF:

0.0187

Gnomad4 EAS

AF:

0.0361

Gnomad4 SAS

AF:

0.0534

Gnomad4 FIN

AF:

0.0858

Gnomad4 NFE

AF:

0.0651

Gnomad4 OTH

AF:

0.0478

Alfa

AF:

0.0575

Hom.:

428

Bravo

AF:

0.0465

TwinsUK

AF:

0.0599

AC:

222

ALSPAC

AF:

0.0612

AC:

236

ESP6500AA

AF:

0.0146

AC:

ESP6500EA

AF:

0.0647

AC:

556

ExAC

AF:

0.0583

AC:

7073

Asia WGS

AF:

0.0500

AC:

174

AN:

3478

EpiCase

AF:

0.0567

EpiControl

AF:

0.0583

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group P

Benign:2

Aug 12, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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. -

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

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fanconi anemia

Benign:1

Feb 17, 2023

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

0.12

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.054

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0018

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.6

REVEL

Benign

0.027

Sift

Uncertain

0.019

Sift4G

Uncertain

0.045

Polyphen

0.93

Vest4

0.033

MPC

0.072

ClinPred

0.010

GERP RS

3.2

Varity_R

0.039

gMVP

0.15

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