9-81947593-C-G

Variant names:

• chr9-81947593-C-G
• rs746925793
• NM_207416.3:c.2340C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_207416.3(SPATA31D3):​c.2340C>G​(p.Asn780Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000301 in 1,428,182 control chromosomes in the GnomAD database, including 6 homozygotes. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00028 (4 hom., cov: 22)
  • Exomes 𝑓: 0.000030 (6 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPATA31D3 NM_207416.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.77
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008125693).
• BS2: High Homozygotes in GnomAdExome4 at 6 gene

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.2340C>G	p.Asn780Lys	missense	Exon 4 of 4	NP_997299.2	P0C874
	LOC105376105	NR_188610.1		n.943-1107G>C		intron	N/A
	LOC105376105	NR_188611.1		n.943-1107G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31D3	ENST00000445385.3	TSL:1 MANE Select	c.2340C>G	p.Asn780Lys	missense	Exon 4 of 4	ENSP00000488117.1	P0C874
	ENSG00000267559	ENST00000585776.5	TSL:2	n.943-1107G>C		intron	N/A
	ENSG00000267559	ENST00000592744.1	TSL:4	n.519-1107G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000276 AC: 39 AN: 141066 Hom.: 4 Cov.: 22

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000146

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000110 AC: 26 AN: 236092 AF XY: 0.0000622

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.000160

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000301 AC: 43 AN: 1428182 Hom.: 6 Cov.: 31 AF XY: 0.0000239 AC XY: 17 AN XY: 710504

African (AFR) AF: 0.00107 AC: 34 AN: 31694

American (AMR) AF: 0.0000970 AC: 4 AN: 41240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25696

East Asian (EAS) AF: 0.00 AC: 0 AN: 38132

South Asian (SAS) AF: 0.00 AC: 0 AN: 84308

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5656

European-Non Finnish (NFE) AF: 9.18e-7 AC: 1 AN: 1089734

Other (OTH) AF: 0.0000676 AC: 4 AN: 59150

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000276 AC: 39 AN: 141066 Hom.: 4 Cov.: 22 AF XY: 0.000248 AC XY: 17 AN XY: 68630

African (AFR) AF: 0.00101 AC: 37 AN: 36560

American (AMR) AF: 0.000146 AC: 2 AN: 13684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3348

East Asian (EAS) AF: 0.00 AC: 0 AN: 4632

South Asian (SAS) AF: 0.00 AC: 0 AN: 4348

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9980

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65370

Other (OTH) AF: 0.00 AC: 0 AN: 1936

Alfa AF: 0.0000712 Hom.: 0

ExAC AF: 0.000102 AC: 12

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	0.14
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.013
DANN	Benign	0.23
DEOGEN2	Benign	0.0076	T
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.0081	T
MutationAssessor	Benign	1.0	L
PhyloP100		-2.8
PrimateAI	Benign	0.41	T
Sift4G	Benign	0.26	T
Polyphen		0.050	B
Vest4		0.037
GERP RS		-1.4
Varity_R		0.046
gMVP		0.034
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: rs746925793; hg19: chr9-84562508;