rs115694169

Positions:

chr16-3600989-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_032444.4(SLX4):c.1153C>A(p.Pro385Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.003 in 1,613,620 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0092 ( 20 hom., cov: 31)

Exomes 𝑓: 0.0024 ( 20 hom. )

Consequence

SLX4
NM_032444.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.209

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:

SLX4 (HGNC:):

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=0.0049327016).

BP6

Variant 16-3600989-G-T is Benign according to our data. Variant chr16-3600989-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 262031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-3600989-G-T is described in Lovd as [Benign]. Variant chr16-3600989-G-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00918 (1397/152196) while in subpopulation AFR AF= 0.0277 (1151/41504). AF 95% confidence interval is 0.0264. There are 20 homozygotes in gnomad4. There are 645 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLX4	NM_032444.4 linkuse as main transcript	c.1153C>A	p.Pro385Thr	missense_variant	5/15	ENST00000294008.4	NP_115820.2	Q8IY92-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLX4	ENST00000294008.4 linkuse as main transcript	c.1153C>A	p.Pro385Thr	missense_variant	5/15	5	NM_032444.4	ENSP00000294008.3	Q8IY92-1
SLX4	ENST00000466154.5 linkuse as main transcript	n.2374C>A		non_coding_transcript_exon_variant	3/7	1
SLX4	ENST00000486524.1 linkuse as main transcript	n.2707C>A		non_coding_transcript_exon_variant	4/4	2
SLX4	ENST00000697858.1 linkuse as main transcript	n.494C>A		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes

AF:

0.00915

AC:

1392

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0277

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00537

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00179

Gnomad OTH

AF:

0.00911

GnomAD3 exomes

AF:

0.00376

AC:

942

AN:

250206

Hom.:

AF XY:

0.00318

AC XY:

431

AN XY:

135458

show subpopulations

Gnomad AFR exome

AF:

0.0280

Gnomad AMR exome

AF:

0.00463

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00252

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00185

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00236

AC:

3449

AN:

1461424

Hom.:

Cov.:

AF XY:

0.00231

AC XY:

1678

AN XY:

727024

show subpopulations

Gnomad4 AFR exome

AF:

0.0291

Gnomad4 AMR exome

AF:

0.00454

Gnomad4 ASJ exome

AF:

0.00134

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00314

Gnomad4 FIN exome

AF:

0.000301

Gnomad4 NFE exome

AF:

0.00149

Gnomad4 OTH exome

AF:

0.00361

GnomAD4 genome

AF:

0.00918

AC:

1397

AN:

152196

Hom.:

Cov.:

AF XY:

0.00867

AC XY:

645

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0277

Gnomad4 AMR

AF:

0.00536

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00353

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00179

Gnomad4 OTH

AF:

0.00901

Alfa

AF:

0.00560

Hom.:

Bravo

AF:

0.00987

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.0207

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.00432

AC:

524

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00354

EpiControl

AF:

0.00279

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Likely benign, no assertion criteria provided	curation	Leiden Open Variation Database	Aug 31, 2012	Curator: Arleen D. Auerbach. Submitter to LOVD: Janine Bakker. -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Fanconi anemia complementation group P

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -

Fanconi anemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.48

DANN

Benign

0.37

DEOGEN2

Benign

0.052

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.27

MetaRNN

Benign

0.0049

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.1

REVEL

Benign

0.044

Sift

Benign

0.45

Sift4G

Benign

0.38

Polyphen

0.031

Vest4

0.054

MVP

0.12

MPC

0.15

ClinPred

0.0020

GERP RS

0.013

Varity_R

0.034

gMVP

0.24

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