9-81932413-G-A

Variant names:

• chr9-81932413-G-A
• NM_001145197.1:c.2252G>A

Variant summary

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

The NM_001145197.1(SPATA31D4):​c.2252G>A​(p.Arg751Lys) 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. 9/12 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: 14)
• Consequence: SPATA31D4 NM_001145197.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0310

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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05997923).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31D4	NM_001145197.1	c.2252G>A	p.Arg751Lys	missense_variant	Exon 4 of 4	ENST00000419782.5	NP_001138669.1
LOC105376105	NR_188610.1	n.1040-1019C>T		intron_variant	Intron 4 of 5
LOC105376105	NR_188611.1	n.1229-1019C>T		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA31D4	ENST00000419782.5	c.2252G>A	p.Arg751Lys	missense_variant	Exon 4 of 4	1	NM_001145197.1	ENSP00000488251.1
ENSG00000267559	ENST00000585776.5	n.1040-1019C>T		intron_variant	Intron 4 of 4	2

Frequencies

GnomAD3 genomes Cov.: 14

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 14

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.2252G>A (p.R751K) 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 2252, causing the arginine (R) at amino acid position 751 to be replaced by a lysine (K). 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	0.11
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.47
DANN	Benign	0.60
DEOGEN2	Benign	0.0049	T
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.060	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.36	T
Sift4G	Benign	1.0	T
Polyphen		0.034	B
Vest4		0.074
GERP RS		0.67
Varity_R		0.27
gMVP		0.061

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: chr9-84547328;