NM_001145197.1:c.2252G>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R751S) has been classified as Uncertain significance.

• 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
• Publications: 0 publications found

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

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=0.05997923).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145197.1. 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
	SPATA31D4	NM_001145197.1	MANE Select	c.2252G>A	p.Arg751Lys	missense	Exon 4 of 4	NP_001138669.1	Q6ZUB0
	LOC105376105	NR_188610.1		n.1040-1019C>T		intron	N/A
	LOC105376105	NR_188611.1		n.1229-1019C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31D4	ENST00000419782.5	TSL:1 MANE Select	c.2252G>A	p.Arg751Lys	missense	Exon 4 of 4	ENSP00000488251.1	Q6ZUB0
	ENSG00000267559	ENST00000585776.5	TSL:2	n.1040-1019C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 14

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 14

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		0.031
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
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

hg19: chr9-84547328;