chr9-81947583-C-T

Variant names:

• chr9-81947583-C-T
• rs933102520
• NM_207416.3:c.2330C>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.2330C>T​(p.Ala777Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000281 in 1,425,636 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000043 (0 hom., cov: 22)
  • Exomes 𝑓: 0.0000028 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPATA31D3 NM_207416.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.22
• 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=0.044935524).

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.2330C>T	p.Ala777Val	missense	Exon 4 of 4	NP_997299.2	P0C874
	LOC105376105	NR_188610.1		n.943-1097G>A		intron	N/A
	LOC105376105	NR_188611.1		n.943-1097G>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.2330C>T	p.Ala777Val	missense	Exon 4 of 4	ENSP00000488117.1	P0C874
	ENSG00000267559	ENST00000585776.5	TSL:2	n.943-1097G>A		intron	N/A
	ENSG00000267559	ENST00000592744.1	TSL:4	n.519-1097G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000430 AC: 6 AN: 139538 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000167

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00000435 AC: 1 AN: 229846 AF XY: 0.00

Gnomad AFR exome AF: 0.0000740

Gnomad AMR exome AF: 0.00

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: 0.00000281 AC: 4 AN: 1425636 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 708924

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000947 AC: 3 AN: 31686

American (AMR) AF: 0.00 AC: 0 AN: 40764

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25662

East Asian (EAS) AF: 0.00 AC: 0 AN: 38046

South Asian (SAS) AF: 0.00 AC: 0 AN: 83796

European-Finnish (FIN) AF: 0.0000191 AC: 1 AN: 52424

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5654

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1088506

Other (OTH) AF: 0.00 AC: 0 AN: 59098

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00209061), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000430 AC: 6 AN: 139538 Hom.: 0 Cov.: 22 AF XY: 0.0000442 AC XY: 3 AN XY: 67810

African (AFR) AF: 0.000167 AC: 6 AN: 36030

American (AMR) AF: 0.00 AC: 0 AN: 13482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3338

East Asian (EAS) AF: 0.00 AC: 0 AN: 4580

South Asian (SAS) AF: 0.00 AC: 0 AN: 4274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64860

Other (OTH) AF: 0.00 AC: 0 AN: 1916

Alfa AF: 0.0000712 Hom.: 0

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	0.075
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.20
DANN	Benign	0.53
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.045	T
MutationAssessor	Benign	-0.55	N
PhyloP100		-1.2
PrimateAI	Benign	0.31	T
Sift4G	Benign	0.27	T
Polyphen		0.0	B
Vest4		0.069
GERP RS		-4.0
Varity_R		0.020
gMVP		0.037
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: rs933102520; hg19: chr9-84562498;