9-81932414-A-C

Variant names:

• chr9-81932414-A-C
• NM_001145197.1:c.2253A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145197.1(SPATA31D4):​c.2253A>C​(p.Arg751Ser) 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. 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: 15)
• Consequence: SPATA31D4 NM_001145197.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.27

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08143327).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31D4	NM_001145197.1	c.2253A>C	p.Arg751Ser	missense_variant	Exon 4 of 4	ENST00000419782.5	NP_001138669.1
LOC105376105	NR_188610.1	n.1040-1020T>G		intron_variant	Intron 4 of 5
LOC105376105	NR_188611.1	n.1229-1020T>G		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA31D4	ENST00000419782.5	c.2253A>C	p.Arg751Ser	missense_variant	Exon 4 of 4	1	NM_001145197.1	ENSP00000488251.1
ENSG00000267559	ENST00000585776.5	n.1040-1020T>G		intron_variant	Intron 4 of 4	2

Frequencies

GnomAD3 genomes Cov.: 15

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 15

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2253A>C (p.R751S) alteration is located in exon 4 (coding exon 4) of the SPATA31D4 gene. This alteration results from a A to C substitution at nucleotide position 2253, causing the arginine (R) at amino acid position 751 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	0.26
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.3
DANN	Benign	0.61
DEOGEN2	Benign	0.0043	T
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.081	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Benign	0.34	T
Sift4G	Benign	0.25	T
Polyphen		0.092	B
Vest4		0.13
GERP RS		0.67
Varity_R		0.30
gMVP		0.085

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-84547329;