Variant 16-3589855-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032444.4(SLX4):c.3783G>A(p.Pro1261Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00552 in 1,612,906 control chromosomes in the GnomAD database, including 221 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 121 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 100 hom. )

Consequence

SLX4
NM_032444.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -8.02

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 16-3589855-C-T is Benign according to our data. Variant chr16-3589855-C-T is described in ClinVar as [Benign]. Clinvar id is 262049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-3589855-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-8.02 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLX4	NM_032444.4 linkuse as main transcript	c.3783G>A	p.Pro1261Pro	synonymous_variant	12/15	ENST00000294008.4	NP_115820.2	Q8IY92-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLX4	ENST00000294008.4 linkuse as main transcript	c.3783G>A	p.Pro1261Pro	synonymous_variant	12/15	5	NM_032444.4	ENSP00000294008.3		Q8IY92-1

Frequencies

GnomAD3 genomes

AF:

0.0212

AC:

3227

AN:

152114

Hom.:

120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0683

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00982

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00622

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00226

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.00745

AC:

1843

AN:

247436

Hom.:

AF XY:

0.00595

AC XY:

800

AN XY:

134524

show subpopulations

Gnomad AFR exome

AF:

0.0710

Gnomad AMR exome

AF:

0.00676

Gnomad ASJ exome

AF:

0.00460

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00448

Gnomad FIN exome

AF:

0.000193

Gnomad NFE exome

AF:

0.00256

Gnomad OTH exome

AF:

0.00614

GnomAD4 exome

AF:

0.00387

AC:

5660

AN:

1460674

Hom.:

100

Cov.:

AF XY:

0.00379

AC XY:

2754

AN XY:

726694

show subpopulations

Gnomad4 AFR exome

AF:

0.0663

Gnomad4 AMR exome

AF:

0.00722

Gnomad4 ASJ exome

AF:

0.00394

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00557

Gnomad4 FIN exome

AF:

0.000401

Gnomad4 NFE exome

AF:

0.00173

Gnomad4 OTH exome

AF:

0.00772

GnomAD4 genome

AF:

0.0213

AC:

3236

AN:

152232

Hom.:

121

Cov.:

AF XY:

0.0204

AC XY:

1516

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0684

Gnomad4 AMR

AF:

0.00981

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00581

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00226

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.00207

Hom.:

Bravo

AF:

0.0240

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.00480

EpiControl

AF:

0.00367

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jan 13, 2017	- -
Likely benign, no assertion criteria provided	curation	Leiden Open Variation Database	Aug 31, 2012	Curator: Arleen D. Auerbach. Submitter to LOVD: Janine Bakker. -

Fanconi anemia complementation group P

Benign:2

Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 16, 2019	- -

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

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.067

DANN

Benign

0.79

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