chr9-81932491-C-A

Variant names:

• chr9-81932491-C-A
• rs1426570808
• NM_001145197.1:c.2330C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001145197.1(SPATA31D4):​c.2330C>A​(p.Ala777Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPATA31D4 NM_001145197.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.90
• Publications: 0 publications found

Genes affected

SPATA31D4 (HGNC:38601): (SPATA31 subfamily D member 4) Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267559 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05883804).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145197.1. 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
	SPATA31D4	NM_001145197.1	MANE Select	c.2330C>A	p.Ala777Asp	missense	Exon 4 of 4	NP_001138669.1	Q6ZUB0
	LOC105376105	NR_188610.1		n.1040-1097G>T		intron	N/A
	LOC105376105	NR_188611.1		n.1229-1097G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31D4	ENST00000419782.5	TSL:1 MANE Select	c.2330C>A	p.Ala777Asp	missense	Exon 4 of 4	ENSP00000488251.1	Q6ZUB0
	ENSG00000267559	ENST00000585776.5	TSL:2	n.1040-1097G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.38e-7 AC: 1 AN: 1354232 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 674544

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30464

American (AMR) AF: 0.00 AC: 0 AN: 40128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24844

East Asian (EAS) AF: 0.00 AC: 0 AN: 38956

South Asian (SAS) AF: 0.00 AC: 0 AN: 83174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48812

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5408

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1026174

Other (OTH) AF: 0.0000178 AC: 1 AN: 56272

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 19

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.049
DANN	Benign	0.29
DEOGEN2	Benign	0.0081	T
FATHMM_MKL	Benign	0.0012	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.059	T
MutationAssessor	Benign	0.34	N
PhyloP100		-1.9
PrimateAI	Benign	0.34	T
Sift4G	Benign	0.094	T
Polyphen		0.15	B
Vest4		0.12
GERP RS		-1.5
Varity_R		0.11
gMVP		0.077
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: rs1426570808; hg19: chr9-84547406;