rs28516461

Positions:

Variant summary

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

The NM_032444.4(SLX4):c.678C>T(p.His226=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0356 in 1,614,068 control chromosomes in the GnomAD database, including 3,877 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.089 ( 1447 hom., cov: 32)

Exomes 𝑓: 0.030 ( 2430 hom. )

Consequence

SLX4
NM_032444.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.120

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 16-3606556-G-A is Benign according to our data. Variant chr16-3606556-G-A is described in ClinVar as [Benign]. Clinvar id is 262057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-3606556-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.12 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLX4	NM_032444.4 linkuse as main transcript	c.678C>T	p.His226=	synonymous_variant	3/15	ENST00000294008.4	NP_115820.2
SLX4	XM_024450471.2 linkuse as main transcript	c.678C>T	p.His226=	synonymous_variant	3/15		XP_024306239.1
SLX4	XM_011522715.4 linkuse as main transcript	c.678C>T	p.His226=	synonymous_variant	3/15		XP_011521017.1
SLX4	XR_007064923.1 linkuse as main transcript	n.1327C>T		non_coding_transcript_exon_variant	3/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLX4	ENST00000294008.4 linkuse as main transcript	c.678C>T	p.His226=	synonymous_variant	3/15	5	NM_032444.4	ENSP00000294008	P1	Q8IY92-1
SLX4	ENST00000466154.5 linkuse as main transcript	n.973C>T		non_coding_transcript_exon_variant	2/7	1
SLX4	ENST00000486524.1 linkuse as main transcript	n.1306C>T		non_coding_transcript_exon_variant	3/4	2
SLX4	ENST00000697858.1 linkuse as main transcript	n.19C>T		non_coding_transcript_exon_variant	1/3

Frequencies

GnomAD3 genomes

AF:

0.0889

AC:

13520

AN:

152064

Hom.:

1444

Cov.:

show subpopulations

Gnomad AFR

AF:

0.253

Gnomad AMI

AF:

0.0209

Gnomad AMR

AF:

0.0525

Gnomad ASJ

AF:

0.0366

Gnomad EAS

AF:

0.0457

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.0134

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0136

Gnomad OTH

AF:

0.0843

GnomAD3 exomes

AF:

0.0492

AC:

12359

AN:

251426

Hom.:

887

AF XY:

0.0493

AC XY:

6697

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.260

Gnomad AMR exome

AF:

0.0270

Gnomad ASJ exome

AF:

0.0314

Gnomad EAS exome

AF:

0.0512

Gnomad SAS exome

AF:

0.124

Gnomad FIN exome

AF:

0.0144

Gnomad NFE exome

AF:

0.0141

Gnomad OTH exome

AF:

0.0379

GnomAD4 exome

AF:

0.0300

AC:

43897

AN:

1461888

Hom.:

2430

Cov.:

AF XY:

0.0321

AC XY:

23323

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.276

Gnomad4 AMR exome

AF:

0.0289

Gnomad4 ASJ exome

AF:

0.0314

Gnomad4 EAS exome

AF:

0.0482

Gnomad4 SAS exome

AF:

0.123

Gnomad4 FIN exome

AF:

0.0133

Gnomad4 NFE exome

AF:

0.0145

Gnomad4 OTH exome

AF:

0.0457

GnomAD4 genome

AF:

0.0890

AC:

13537

AN:

152180

Hom.:

1447

Cov.:

AF XY:

0.0890

AC XY:

6625

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.253

Gnomad4 AMR

AF:

0.0524

Gnomad4 ASJ

AF:

0.0366

Gnomad4 EAS

AF:

0.0460

Gnomad4 SAS

AF:

0.125

Gnomad4 FIN

AF:

0.0134

Gnomad4 NFE

AF:

0.0136

Gnomad4 OTH

AF:

0.0834

Alfa

AF:

0.0392

Hom.:

238

Bravo

AF:

0.0993

Asia WGS

AF:

0.105

AC:

363

AN:

3478

EpiCase

AF:

0.0181

EpiControl

AF:

0.0191

ClinVar

Significance: Benign

Submissions summary: Benign:8

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, 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	Apr 04, 2017	- -

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 13, 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	clinical testing	GeneDx	Mar 25, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.87

CADD

Benign

0.98

DANN

Benign

0.89

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