9-81947580-C-T

Variant names:

• chr9-81947580-C-T
• rs1462222560
• NM_207416.3:c.2327C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_207416.3(SPATA31D3):​c.2327C>T​(p.Thr776Ile) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T776S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 22)
• Consequence: SPATA31D3 NM_207416.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.605
• Publications: 0 publications found

Genes affected

SPATA31D3 (HGNC:38603): (SPATA31 subfamily D member 3) 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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05481282).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207416.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31D3	NM_207416.3	MANE Select	c.2327C>T	p.Thr776Ile	missense	Exon 4 of 4	NP_997299.2	P0C874
	LOC105376105	NR_188610.1		n.943-1094G>A		intron	N/A
	LOC105376105	NR_188611.1		n.943-1094G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31D3	ENST00000445385.3	TSL:1 MANE Select	c.2327C>T	p.Thr776Ile	missense	Exon 4 of 4	ENSP00000488117.1	P0C874
	ENSG00000267559	ENST00000585776.5	TSL:2	n.943-1094G>A		intron	N/A
	ENSG00000267559	ENST00000592744.1	TSL:4	n.519-1094G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.14
DANN	Benign	0.55
DEOGEN2	Benign	0.012	T
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.055	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.60
PrimateAI	Benign	0.47	T
Sift4G	Uncertain	0.0080	D
Polyphen		0.40	B
Vest4		0.069
GERP RS		-4.0
Varity_R		0.031
gMVP		0.045
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1462222560; hg19: chr9-84562495; COSMIC: COSV61986517;