rs3810812

Variant names:

• chr16-3589138-A-G
• rs3810812
• NM_032444.4:c.4500T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-3589138-A-G
• chr16-3589138-A-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_032444.4(SLX4):​c.4500T>C​(p.Asn1500Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 1,613,870 control chromosomes in the GnomAD database, including 256,101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (33045 hom., cov: 31)
  • Exomes 𝑓: 0.54 (223056 hom.)
• Consequence: SLX4 NM_032444.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.753
• Publications: 37 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: ClinGen, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• familial ovarian cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-3589138-A-G is Benign according to our data. Variant chr16-3589138-A-G is described in ClinVar as Benign. ClinVar VariationId is 262053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.753 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLX4	NM_032444.4	MANE Select	c.4500T>C	p.Asn1500Asn	synonymous	Exon 12 of 15	NP_115820.2	Q8IY92-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLX4	ENST00000294008.4	TSL:5 MANE Select	c.4500T>C	p.Asn1500Asn	synonymous	Exon 12 of 15	ENSP00000294008.3	Q8IY92-1

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96966 AN: 151922 Hom.: 32978 Cov.: 31

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.611

GnomAD2 exomes AF: 0.604 AC: 151712 AN: 251234 AF XY: 0.602

Gnomad AFR exome AF: 0.878

Gnomad AMR exome AF: 0.669

Gnomad ASJ exome AF: 0.487

Gnomad EAS exome AF: 0.720

Gnomad FIN exome AF: 0.515

Gnomad NFE exome AF: 0.513

Gnomad OTH exome AF: 0.559

GnomAD4 exome AF: 0.544 AC: 795369 AN: 1461830 Hom.: 223056 Cov.: 83 AF XY: 0.549 AC XY: 399049 AN XY: 727216

African (AFR) AF: 0.892 AC: 29870 AN: 33480

American (AMR) AF: 0.657 AC: 29363 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 12600 AN: 26136

East Asian (EAS) AF: 0.738 AC: 29280 AN: 39700

South Asian (SAS) AF: 0.758 AC: 65422 AN: 86258

European-Finnish (FIN) AF: 0.517 AC: 27614 AN: 53372

Middle Eastern (MID) AF: 0.561 AC: 3237 AN: 5766

European-Non Finnish (NFE) AF: 0.507 AC: 564179 AN: 1111998

Other (OTH) AF: 0.560 AC: 33804 AN: 60396

GnomAD4 genome AF: 0.639 AC: 97099 AN: 152040 Hom.: 33045 Cov.: 31 AF XY: 0.642 AC XY: 47715 AN XY: 74302

African (AFR) AF: 0.875 AC: 36318 AN: 41512

American (AMR) AF: 0.619 AC: 9466 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1692 AN: 3466

East Asian (EAS) AF: 0.716 AC: 3696 AN: 5162

South Asian (SAS) AF: 0.774 AC: 3733 AN: 4826

European-Finnish (FIN) AF: 0.515 AC: 5438 AN: 10558

Middle Eastern (MID) AF: 0.620 AC: 181 AN: 292

European-Non Finnish (NFE) AF: 0.512 AC: 34782 AN: 67922

Other (OTH) AF: 0.616 AC: 1301 AN: 2112

Alfa AF: 0.552 Hom.: 108453

Bravo AF: 0.654

Asia WGS AF: 0.759 AC: 2640 AN: 3478

EpiCase AF: 0.513

EpiControl AF: 0.517

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Fanconi anemia complementation group P (4)
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Fanconi anemia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.35
PhyloP100		0.75
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: rs3810812; hg19: chr16-3639139; COSMIC: COSV53564459;