rs75693937

Positions:

• chr16-3585098-G-A
• chr16-3585098-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032444.4(SLX4):​c.4637-227C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0575 in 152,176 control chromosomes in the GnomAD database, including 275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.058 (275 hom., cov: 32)
• Consequence: SLX4 NM_032444.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.649

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-3585098-G-A is Benign according to our data. Variant chr16-3585098-G-A is described in ClinVar as [Benign]. Clinvar id is 929609.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-3585098-G-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.064 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLX4	NM_032444.4	c.4637-227C>T		intron_variant		ENST00000294008.4	NP_115820.2
SLX4	XM_024450471.2	c.4637-227C>T		intron_variant			XP_024306239.1
SLX4	XM_011522715.4	c.4637-230C>T		intron_variant			XP_011521017.1
SLX4	XM_047434801.1	c.3635-227C>T		intron_variant			XP_047290757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLX4	ENST00000294008.4	c.4637-227C>T		intron_variant		5	NM_032444.4	ENSP00000294008.3

Frequencies

GnomAD3 genomes AF: 0.0576 AC: 8754 AN: 152058 Hom.: 274 Cov.: 32

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.0596

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.0318

Gnomad SAS AF: 0.0521

Gnomad FIN AF: 0.0865

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0656

Gnomad OTH AF: 0.0537

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0575 AC: 8754 AN: 152176 Hom.: 275 Cov.: 32 AF XY: 0.0587 AC XY: 4365 AN XY: 74386

Gnomad4 AFR AF: 0.0429

Gnomad4 AMR AF: 0.0596

Gnomad4 ASJ AF: 0.0187

Gnomad4 EAS AF: 0.0319

Gnomad4 SAS AF: 0.0529

Gnomad4 FIN AF: 0.0865

Gnomad4 NFE AF: 0.0656

Gnomad4 OTH AF: 0.0527

Alfa AF: 0.0349 Hom.: 20

Bravo AF: 0.0547

Asia WGS AF: 0.0480 AC: 168 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, no assertion criteria provided

curation

Leiden Open Variation Database

Aug 31, 2012

Curator: Arleen D. Auerbach. Submitter to LOVD: Janine Bakker. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 24, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.78
DANN	Benign	0.56

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

Other links and lift over

dbSNP: rs75693937; hg19: chr16-3635099;