rs541410329

Variant names:

• chr16-3581684-A-G
• rs541410329
• NM_032444.4:c.*658T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_032444.4(SLX4):​c.*658T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00231 in 156,170 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (0 hom.)
• Consequence: SLX4 NM_032444.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.378
• Publications: 0 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: G2P, Labcorp Genetics (formerly Invitae), ClinGen
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-3581684-A-G is Benign according to our data. Variant chr16-3581684-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 319131.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00228 (348/152346) while in subpopulation AMR AF = 0.00346 (53/15306). AF 95% confidence interval is 0.00286. There are 1 homozygotes in GnomAd4. There are 143 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

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.*658T>C		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.*658T>C		3_prime_UTR	Exon 15 of 15	ENSP00000294008.3	Q8IY92-1
	ENSG00000261938	ENST00000573982.1	TSL:3	n.198+306A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00229 AC: 348 AN: 152228 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00320

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00314 AC: 12 AN: 3824 Hom.: 0 Cov.: 0 AF XY: 0.00240 AC XY: 5 AN XY: 2084

African (AFR) AF: 0.00 AC: 0 AN: 28

American (AMR) AF: 0.00127 AC: 1 AN: 786

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18

East Asian (EAS) AF: 0.00 AC: 0 AN: 72

South Asian (SAS) AF: 0.00407 AC: 1 AN: 246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00402 AC: 10 AN: 2486

Other (OTH) AF: 0.00 AC: 0 AN: 144

GnomAD4 genome AF: 0.00228 AC: 348 AN: 152346 Hom.: 1 Cov.: 33 AF XY: 0.00192 AC XY: 143 AN XY: 74504

African (AFR) AF: 0.000601 AC: 25 AN: 41576

American (AMR) AF: 0.00346 AC: 53 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00950 AC: 33 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4832

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10632

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00320 AC: 218 AN: 68030

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00212 Hom.: 0

Bravo AF: 0.00270

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Fanconi anemia complementation group P (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.68
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism

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: rs541410329; hg19: chr16-3631685;