9-88134805-C-T

Variant names:

• chr9-88134805-C-T
• rs753696646
• NM_001350978.3:c.190-1136G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001166137.1(SPATA31C2):​c.152G>A​(p.Cys51Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 4/4 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. C51F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPATA31C2 NM_001166137.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.765
• Publications: 0 publications found

Genes affected

SPATA31C2 (HGNC:24508): (SPATA31 subfamily C member 2) Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000307536 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166137.1. 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
	SPATA31C2	NM_001350978.3	MANE Select	c.190-1136G>A		intron	N/A	NP_001337907.1	A0A8I5KWQ5
	SPATA31C2	NM_001166137.1		c.152G>A	p.Cys51Tyr	missense	Exon 1 of 4	NP_001159609.1	B4DYI2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31C2	ENST00000324915.6	TSL:6 MANE Select	c.190-1136G>A		intron	N/A	ENSP00000509734.1	A0A8I5KWQ5
	SPATA31C2	ENST00000675441.1		c.152G>A	p.Cys51Tyr	missense	Exon 1 of 4	ENSP00000509164.1	B4DYI2
	ENSG00000307536	ENST00000826920.1		n.154+14972C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000467 AC: 1 AN: 213930 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000191

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000208 AC: 3 AN: 1441236 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 716714

⚠️ 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: 32646

American (AMR) AF: 0.00 AC: 0 AN: 42746

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25590

East Asian (EAS) AF: 0.00 AC: 0 AN: 38810

South Asian (SAS) AF: 0.00 AC: 0 AN: 85490

European-Finnish (FIN) AF: 0.0000578 AC: 3 AN: 51874

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4024

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101200

Other (OTH) AF: 0.00 AC: 0 AN: 58856

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0232839), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.36
PhyloP100		0.77
PromoterAI		0.0022	Neutral

Splicing

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

Other links and lift over

dbSNP: rs753696646; hg19: chr9-90749720;