9-81947433-G-C

Variant names:

• chr9-81947433-G-C
• rs779902056
• NM_207416.3:c.2180G>C

Variant summary

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

The NM_207416.3(SPATA31D3):​c.2180G>C​(p.Gly727Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/12 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. G727D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 10)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPATA31D3 NM_207416.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708
• 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=0.17642832).

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.2180G>C	p.Gly727Ala	missense	Exon 4 of 4	NP_997299.2	P0C874
	LOC105376105	NR_188610.1		n.943-947C>G		intron	N/A
	LOC105376105	NR_188611.1		n.943-947C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31D3	ENST00000445385.3	TSL:1 MANE Select	c.2180G>C	p.Gly727Ala	missense	Exon 4 of 4	ENSP00000488117.1	P0C874
	ENSG00000267559	ENST00000585776.5	TSL:2	n.943-947C>G		intron	N/A
	ENSG00000267559	ENST00000592744.1	TSL:4	n.519-947C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 10

GnomAD2 exomes AF: 0.00000943 AC: 1 AN: 106014 AF XY: 0.0000180

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: 0.0000252

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 8.95e-7 AC: 1 AN: 1116878 Hom.: 0 Cov.: 17 AF XY: 0.00000179 AC XY: 1 AN XY: 558706

⚠️ 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: 24764

American (AMR) AF: 0.00 AC: 0 AN: 31220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22248

East Asian (EAS) AF: 0.00 AC: 0 AN: 33326

South Asian (SAS) AF: 0.00 AC: 0 AN: 69532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4444

European-Non Finnish (NFE) AF: 0.00000120 AC: 1 AN: 835750

Other (OTH) AF: 0.00 AC: 0 AN: 48278

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 10

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.2
DANN	Benign	0.39
DEOGEN2	Benign	0.028	T
FATHMM_MKL	Benign	0.0094	N
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.18	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-0.71
PrimateAI	Benign	0.41	T
Sift4G	Benign	0.15	T
Polyphen		0.99	D
Vest4		0.047
GERP RS		0.26
Varity_R		0.035
gMVP		0.038
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: rs779902056; hg19: chr9-84562348;