rs75693937

Variant names:

• chr16-3585098-G-A
• rs75693937
• NM_032444.4:c.4637-227C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group P

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• familial ovarian cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 929609.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.064 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032444.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLX4	NM_032444.4	MANE Select	c.4637-227C>T		intron	N/A	NP_115820.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLX4	ENST00000294008.4	TSL:5 MANE Select	c.4637-227C>T		intron	N/A	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

African (AFR) AF: 0.0429 AC: 1783 AN: 41544

American (AMR) AF: 0.0596 AC: 910 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3468

East Asian (EAS) AF: 0.0319 AC: 165 AN: 5170

South Asian (SAS) AF: 0.0529 AC: 255 AN: 4818

European-Finnish (FIN) AF: 0.0865 AC: 916 AN: 10586

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0656 AC: 4462 AN: 68000

Other (OTH) AF: 0.0527 AC: 111 AN: 2108

Alfa AF: 0.0349 Hom.: 20

Bravo AF: 0.0547

Asia WGS AF: 0.0480 AC: 168 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.78
DANN	Benign	0.56
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs75693937; hg19: chr16-3635099;