chr9-81947502-C-T

Variant names:

• chr9-81947502-C-T
• rs769395407
• NM_207416.3:c.2249C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_207416.3(SPATA31D3):​c.2249C>T​(p.Pro750Leu) 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: 𝑓 0.000018 (0 hom., cov: 19)
  • Exomes 𝑓: 0.000022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPATA31D3 NM_207416.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.551
• 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12279588).

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.2249C>T	p.Pro750Leu	missense	Exon 4 of 4	NP_997299.2	P0C874
	LOC105376105	NR_188610.1		n.943-1016G>A		intron	N/A
	LOC105376105	NR_188611.1		n.943-1016G>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.2249C>T	p.Pro750Leu	missense	Exon 4 of 4	ENSP00000488117.1	P0C874
	ENSG00000267559	ENST00000585776.5	TSL:2	n.943-1016G>A		intron	N/A
	ENSG00000267559	ENST00000592744.1	TSL:4	n.519-1016G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 2 AN: 112114 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.00

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: 0.000143

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000182

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000788 AC: 1 AN: 126974 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.0000207

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000219 AC: 30 AN: 1367066 Hom.: 0 Cov.: 28 AF XY: 0.0000162 AC XY: 11 AN XY: 677952

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

African (AFR) AF: 0.00 AC: 0 AN: 30366

American (AMR) AF: 0.00 AC: 0 AN: 36490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24970

East Asian (EAS) AF: 0.00 AC: 0 AN: 36182

South Asian (SAS) AF: 0.00 AC: 0 AN: 79000

European-Finnish (FIN) AF: 0.0000397 AC: 2 AN: 50422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5560

European-Non Finnish (NFE) AF: 0.0000239 AC: 25 AN: 1046966

Other (OTH) AF: 0.0000525 AC: 3 AN: 57110

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000581424), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000178 AC: 2 AN: 112114 Hom.: 0 Cov.: 19 AF XY: 0.0000187 AC XY: 1 AN XY: 53416

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

African (AFR) AF: 0.00 AC: 0 AN: 28112

American (AMR) AF: 0.00 AC: 0 AN: 10222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2850

East Asian (EAS) AF: 0.00 AC: 0 AN: 3394

South Asian (SAS) AF: 0.00 AC: 0 AN: 2956

European-Finnish (FIN) AF: 0.000143 AC: 1 AN: 7006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 234

European-Non Finnish (NFE) AF: 0.0000182 AC: 1 AN: 55088

Other (OTH) AF: 0.00 AC: 0 AN: 1422

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000116 AC: 1

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	0.13
BayesDel_noAF	Benign	-0.89
CADD	Benign	12
DANN	Benign	0.43
DEOGEN2	Benign	0.021	T
FATHMM_MKL	Benign	0.0095	N
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.12	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.55
PrimateAI	Benign	0.35	T
Sift4G	Uncertain	0.0090	D
Polyphen		0.82	P
Vest4		0.072
GERP RS		1.2
Varity_R		0.051
gMVP		0.072
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: rs769395407; hg19: chr9-84562417;