NM_032444.4:c.610C>T

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.610C>T(p.Arg204Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0637 in 1,614,118 control chromosomes in the GnomAD database, including 3,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.068 ( 366 hom., cov: 32)

Exomes 𝑓: 0.063 ( 3153 hom. )

Consequence

SLX4
NM_032444.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.07

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=0.0026601255).

BP6

Variant 16-3606624-G-A is Benign according to our data. Variant chr16-3606624-G-A is described in ClinVar as [Benign]. Clinvar id is 262056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-3606624-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLX4	NM_032444.4 link	c.610C>T	p.Arg204Cys	missense_variant	Exon 3 of 15	ENST00000294008.4	NP_115820.2	Q8IY92-1
SLX4	XM_024450471.2 link	c.610C>T	p.Arg204Cys	missense_variant	Exon 3 of 15		XP_024306239.1
SLX4	XM_011522715.4 link	c.610C>T	p.Arg204Cys	missense_variant	Exon 3 of 15		XP_011521017.1
SLX4	XR_007064923.1 link	n.1259C>T		non_coding_transcript_exon_variant	Exon 3 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLX4	ENST00000294008.4 link	c.610C>T	p.Arg204Cys	missense_variant	Exon 3 of 15	5	NM_032444.4	ENSP00000294008.3	Q8IY92-1
SLX4	ENST00000466154.5 link	n.905C>T		non_coding_transcript_exon_variant	Exon 2 of 7	1
SLX4	ENST00000486524.1 link	n.1238C>T		non_coding_transcript_exon_variant	Exon 3 of 4	2
SLX4	ENST00000697858.1 link	n.-50C>T		upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.0675

AC:

10274

AN:

152126

Hom.:

366

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0725

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.0757

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.0363

Gnomad SAS

AF:

0.0532

Gnomad FIN

AF:

0.0867

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0656

Gnomad OTH

AF:

0.0622

GnomAD3 exomes

AF:

0.0630

AC:

15838

AN:

251474

Hom.:

582

AF XY:

0.0614

AC XY:

8349

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0738

Gnomad AMR exome

AF:

0.0733

Gnomad ASJ exome

AF:

0.0188

Gnomad EAS exome

AF:

0.0352

Gnomad SAS exome

AF:

0.0522

Gnomad FIN exome

AF:

0.0882

Gnomad NFE exome

AF:

0.0654

Gnomad OTH exome

AF:

0.0521

GnomAD4 exome

AF:

0.0633

AC:

92592

AN:

1461874

Hom.:

3153

Cov.:

AF XY:

0.0626

AC XY:

45515

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0724

Gnomad4 AMR exome

AF:

0.0699

Gnomad4 ASJ exome

AF:

0.0189

Gnomad4 EAS exome

AF:

0.0318

Gnomad4 SAS exome

AF:

0.0534

Gnomad4 FIN exome

AF:

0.0831

Gnomad4 NFE exome

AF:

0.0652

Gnomad4 OTH exome

AF:

0.0598

GnomAD4 genome

AF:

0.0675

AC:

10277

AN:

152244

Hom.:

366

Cov.:

AF XY:

0.0685

AC XY:

5097

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0725

Gnomad4 AMR

AF:

0.0754

Gnomad4 ASJ

AF:

0.0184

Gnomad4 EAS

AF:

0.0362

Gnomad4 SAS

AF:

0.0541

Gnomad4 FIN

AF:

0.0867

Gnomad4 NFE

AF:

0.0656

Gnomad4 OTH

AF:

0.0616

Alfa

AF:

0.0576

Hom.:

427

Bravo

AF:

0.0676

TwinsUK

AF:

0.0612

AC:

227

ALSPAC

AF:

0.0623

AC:

240

ESP6500AA

AF:

0.0781

AC:

343

ESP6500EA

AF:

0.0678

AC:

583

ExAC

AF:

0.0642

AC:

7790

Asia WGS

AF:

0.0540

AC:

190

AN:

3478

EpiCase

AF:

0.0568

EpiControl

AF:

0.0586

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. -

Nov 27, 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

0.23

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.35

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0027

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.5

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.14

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.19

MPC

0.091

ClinPred

0.026

GERP RS

3.1

Varity_R

0.37

gMVP

0.34

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