9-42185736-C-A

Variant names:

• chr9-42185736-C-A
• rs1174262649
• NM_001145196.1:c.289C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145196.1(SPATA31A6):​c.289C>A​(p.Leu97Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000877 in 1,140,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 5/7 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L97F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
• Consequence: SPATA31A6 NM_001145196.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.854
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13911644).

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.289C>A	p.Leu97Ile	missense	Exon 3 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.289C>A	p.Leu97Ile	missense	Exon 3 of 4	ENSP00000329825.6	Q5VVP1
	SPATA31A6	ENST00000496386.1	TSL:5	n.140C>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 8.77e-7 AC: 1 AN: 1140742 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 571934

⚠️ 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: 25478

American (AMR) AF: 0.00 AC: 0 AN: 36164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20314

East Asian (EAS) AF: 0.00 AC: 0 AN: 30746

South Asian (SAS) AF: 0.00 AC: 0 AN: 72332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48088

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3434

European-Non Finnish (NFE) AF: 0.00000117 AC: 1 AN: 856104

Other (OTH) AF: 0.00 AC: 0 AN: 48082

⚠️ 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.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
CADD	Benign	14
DEOGEN2	Benign	0.082	T
LIST_S2	Benign	0.49	T
MetaRNN	Benign	0.14	T
PhyloP100		-0.85
PROVEAN	Benign	-0.76	N
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.023	D
Vest4		0.29
gMVP		0.083

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1174262649;