9-88130449-T-A

Variant names:

• chr9-88130449-T-A
• rs614696
• NM_001350978.3:c.2588A>T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001350978.3(SPATA31C2):​c.2588A>T​(p.Lys863Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000431 in 1,612,890 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (5 hom., cov: 31)
  • Exomes 𝑓: 0.00019 (1 hom.)
• Consequence: SPATA31C2 NM_001350978.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.934

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BS2: High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31C2	NM_001350978.3	c.2588A>T	p.Lys863Met	missense_variant	Exon 4 of 4	ENST00000324915.6	NP_001337907.1
SPATA31C2	NM_001166137.1	c.2588A>T	p.Lys863Met	missense_variant	Exon 4 of 4		NP_001159609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA31C2	ENST00000324915.6	c.2588A>T	p.Lys863Met	missense_variant	Exon 4 of 4	6	NM_001350978.3	ENSP00000509734.1
SPATA31C2	ENST00000675441.1	c.2588A>T	p.Lys863Met	missense_variant	Exon 4 of 4			ENSP00000509164.1

Frequencies

GnomAD3 genomes AF: 0.00273 AC: 416 AN: 152116 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.00940

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.000273 AC: 68 AN: 248808 Hom.: 0 AF XY: 0.000288 AC XY: 39 AN XY: 135208

Gnomad AFR exome AF: 0.00357

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000355

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000191 AC: 279 AN: 1460656 Hom.: 1 Cov.: 36 AF XY: 0.000195 AC XY: 142 AN XY: 726670

Gnomad4 AFR exome AF: 0.00548

Gnomad4 AMR exome AF: 0.000515

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000757

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.0000315

Gnomad4 OTH exome AF: 0.000547

GnomAD4 genome AF: 0.00273 AC: 416 AN: 152234 Hom.: 5 Cov.: 31 AF XY: 0.00277 AC XY: 206 AN XY: 74454

Gnomad4 AFR AF: 0.00937

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000305 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 27, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2588A>T (p.K863M) alteration is located in exon 4 (coding exon 4) of the SPATA31C2 gene. This alteration results from a A to T substitution at nucleotide position 2588, causing the lysine (K) at amino acid position 863 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs614696; hg19: chr9-90745364;