chr9-42183778-A-T

Variant names:

• chr9-42183778-A-T
• rs1829390085
• NM_001145196.1:c.91A>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001145196.1(SPATA31A6):​c.91A>T​(p.Thr31Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000786 in 1,400,202 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T31I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000079 (3 hom.)
• Consequence: SPATA31A6 NM_001145196.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0400
• Publications: 0 publications found

Genes affected

SPATA31A6 (HGNC:32006): (SPATA31 subfamily A member 6) Predicted to enable actin binding activity. Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be located in acrosomal vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14525259).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145196.1. 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
	SPATA31A6	NM_001145196.1	MANE Select	c.91A>T	p.Thr31Ser	missense	Exon 1 of 4	NP_001138668.1	Q5VVP1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31A6	ENST00000332857.7	TSL:1 MANE Select	c.91A>T	p.Thr31Ser	missense	Exon 1 of 4	ENSP00000329825.6	Q5VVP1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000786 AC: 11 AN: 1400202 Hom.: 3 Cov.: 34 AF XY: 0.0000115 AC XY: 8 AN XY: 696828

African (AFR) AF: 0.00 AC: 0 AN: 29262

American (AMR) AF: 0.00 AC: 0 AN: 42832

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24702

East Asian (EAS) AF: 0.00 AC: 0 AN: 37248

South Asian (SAS) AF: 0.00 AC: 0 AN: 82834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3972

European-Non Finnish (NFE) AF: 0.00000838 AC: 9 AN: 1073762

Other (OTH) AF: 0.0000347 AC: 2 AN: 57564

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

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	0.19
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.7
DANN	Benign	0.71
DEOGEN2	Benign	0.081	T
LIST_S2	Benign	0.38	T
MetaRNN	Benign	0.15	T
PhyloP100		-0.040
PROVEAN	Benign	-0.76	N
Sift	Benign	0.037	D
Sift4G	Benign	0.46	T
Vest4		0.38
PromoterAI		0.027	Neutral
gMVP		0.050

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: rs1829390085; hg19: chr9-43630611;