chr16-3582229-G-A

Variant names:

• chr16-3582229-G-A
• rs76661336
• NM_032444.4:c.*113C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032444.4(SLX4):​c.*113C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0583 in 840,902 control chromosomes in the GnomAD database, including 1,658 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (241 hom., cov: 32)
  • Exomes 𝑓: 0.060 (1417 hom.)
• Consequence: SLX4 NM_032444.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0920
• Publications: 6 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

ENSG00000261938 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 16-3582229-G-A is Benign according to our data. Variant chr16-3582229-G-A is described in ClinVar as Benign. ClinVar VariationId is 319141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0652 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.*113C>T		3_prime_UTR	Exon 15 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.*113C>T		3_prime_UTR	Exon 15 of 15	ENSP00000294008.3	Q8IY92-1
	ENSG00000261938	ENST00000573982.1	TSL:3	n.198+851G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0504 AC: 7572 AN: 150098 Hom.: 241 Cov.: 32

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0690

Gnomad ASJ AF: 0.0188

Gnomad EAS AF: 0.0372

Gnomad SAS AF: 0.0545

Gnomad FIN AF: 0.0910

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.0655

Gnomad OTH AF: 0.0488

GnomAD4 exome AF: 0.0600 AC: 41466 AN: 690698 Hom.: 1417 Cov.: 9 AF XY: 0.0595 AC XY: 21300 AN XY: 358018

African (AFR) AF: 0.0100 AC: 186 AN: 18548

American (AMR) AF: 0.0648 AC: 2091 AN: 32290

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 334 AN: 17820

East Asian (EAS) AF: 0.0318 AC: 1038 AN: 32622

South Asian (SAS) AF: 0.0532 AC: 3066 AN: 57664

European-Finnish (FIN) AF: 0.0813 AC: 2561 AN: 31488

Middle Eastern (MID) AF: 0.0286 AC: 74 AN: 2588

European-Non Finnish (NFE) AF: 0.0654 AC: 30274 AN: 463050

Other (OTH) AF: 0.0532 AC: 1842 AN: 34628

GnomAD4 genome AF: 0.0504 AC: 7568 AN: 150204 Hom.: 241 Cov.: 32 AF XY: 0.0519 AC XY: 3801 AN XY: 73298

African (AFR) AF: 0.0120 AC: 491 AN: 40982

American (AMR) AF: 0.0687 AC: 1040 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.0188 AC: 65 AN: 3450

East Asian (EAS) AF: 0.0371 AC: 186 AN: 5018

South Asian (SAS) AF: 0.0554 AC: 261 AN: 4710

European-Finnish (FIN) AF: 0.0910 AC: 913 AN: 10036

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.0655 AC: 4426 AN: 67594

Other (OTH) AF: 0.0479 AC: 100 AN: 2088

Alfa AF: 0.0598 Hom.: 51

Bravo AF: 0.0465

Asia WGS AF: 0.0510 AC: 179 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.9
DANN	Benign	0.73
PhyloP100		0.092
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: rs76661336; hg19: chr16-3632230;