9-81932616-G-A

Variant names:

• chr9-81932616-G-A
• rs750397437
• NM_001145197.1:c.2455G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001145197.1(SPATA31D4):​c.2455G>A​(p.Gly819Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.000012 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPATA31D4 NM_001145197.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.667

Genes affected

SPATA31D4 (HGNC:38601): (SPATA31 subfamily D member 4) Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267559 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12592143).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31D4	NM_001145197.1	c.2455G>A	p.Gly819Ser	missense_variant	Exon 4 of 4	ENST00000419782.5	NP_001138669.1
LOC105376105	NR_188610.1	n.1040-1222C>T		intron_variant	Intron 4 of 5
LOC105376105	NR_188611.1	n.1229-1222C>T		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA31D4	ENST00000419782.5	c.2455G>A	p.Gly819Ser	missense_variant	Exon 4 of 4	1	NM_001145197.1	ENSP00000488251.1
ENSG00000267559	ENST00000585776.5	n.1040-1222C>T		intron_variant	Intron 4 of 4	2

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD3 exomes AF: 0.0000267 AC: 5 AN: 187264 Hom.: 0 AF XY: 0.0000399 AC XY: 4 AN XY: 100366

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 SAS exome AF: 0.000201

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000116 AC: 16 AN: 1378152 Hom.: 2 Cov.: 30 AF XY: 0.0000117 AC XY: 8 AN XY: 686030

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: 0.000144

Gnomad4 FIN exome AF: 0.0000198

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000349

GnomAD4 genome Cov.: 20

ExAC AF: 0.0000443 AC: 5

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2455G>A (p.G819S) alteration is located in exon 4 (coding exon 4) of the SPATA31D4 gene. This alteration results from a G to A substitution at nucleotide position 2455, causing the glycine (G) at amino acid position 819 to be replaced by a serine (S). 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
AlphaMissense	Benign	0.13
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.7
DANN	Benign	0.58
DEOGEN2	Benign	0.0040	T
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.13	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.46	T
Sift4G	Benign	0.35	T
Polyphen		0.97	D
Vest4		0.060
GERP RS		-1.7
Varity_R		0.050
gMVP		0.064

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

Publications

LitVar

Other links and lift over

dbSNP: rs750397437; hg19: chr9-84547531;