9-81932491-C-A

Variant names:

• chr9-81932491-C-A
• NM_001145197.1:c.2330C>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001145197.1(SPATA31D4):​c.2330C>A​(p.Ala777Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPATA31D4 NM_001145197.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.90

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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05883804).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31D4	NM_001145197.1	c.2330C>A	p.Ala777Asp	missense_variant	Exon 4 of 4	ENST00000419782.5	NP_001138669.1
LOC105376105	NR_188610.1	n.1040-1097G>T		intron_variant	Intron 4 of 5
LOC105376105	NR_188611.1	n.1229-1097G>T		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA31D4	ENST00000419782.5	c.2330C>A	p.Ala777Asp	missense_variant	Exon 4 of 4	1	NM_001145197.1	ENSP00000488251.1
ENSG00000267559	ENST00000585776.5	n.1040-1097G>T		intron_variant	Intron 4 of 4	2

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.38e-7 AC: 1 AN: 1354232 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 674544

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: 0.00

Gnomad4 OTH exome AF: 0.0000178

GnomAD4 genome Cov.: 19

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2330C>A (p.A777D) alteration is located in exon 4 (coding exon 4) of the SPATA31D4 gene. This alteration results from a C to A substitution at nucleotide position 2330, causing the alanine (A) at amino acid position 777 to be replaced by an aspartic acid (D). 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	0.098
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.049
DANN	Benign	0.29
DEOGEN2	Benign	0.0081	T
FATHMM_MKL	Benign	0.0012	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.059	T
MutationAssessor	Benign	0.34	N
PrimateAI	Benign	0.34	T
Sift4G	Benign	0.094	T
Polyphen		0.15	B
Vest4		0.12
GERP RS		-1.5
Varity_R		0.11
gMVP		0.077

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: chr9-84547406;