9-88130176-T-A

Variant names:

• chr9-88130176-T-A
• NM_001350978.3:c.2861A>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001350978.3(SPATA31C2):​c.2861A>T​(p.His954Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPATA31C2 NM_001350978.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.882

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31C2	NM_001350978.3	c.2861A>T	p.His954Leu	missense_variant	Exon 4 of 4	ENST00000324915.6	NP_001337907.1
SPATA31C2	NM_001166137.1	c.2861A>T	p.His954Leu	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.2861A>T	p.His954Leu	missense_variant	Exon 4 of 4	6	NM_001350978.3	ENSP00000509734.1
SPATA31C2	ENST00000675441.1	c.2861A>T	p.His954Leu	missense_variant	Exon 4 of 4			ENSP00000509164.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.87e-7 AC: 1 AN: 1456662 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 724522

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 13, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2861A>T (p.H954L) 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 2861, causing the histidine (H) at amino acid position 954 to be replaced by a leucine (L). 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	-0.95
CADD	Benign	1.0
DANN	Benign	0.57

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-90745091;