9-81945214-T-C

Variant names:

• chr9-81945214-T-C
• rs763508588
• NM_207416.3:c.275T>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_207416.3(SPATA31D3):​c.275T>C​(p.Leu92Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000045 (0 hom., cov: 12)
  • Exomes 𝑓: 0.000037 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPATA31D3 NM_207416.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.746
• 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.34512714).

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.275T>C	p.Leu92Pro	missense	Exon 3 of 4	NP_997299.2	P0C874
	LOC105376105	NR_188610.1		n.1039+1176A>G		intron	N/A
	LOC105376105	NR_188611.1		n.1228+987A>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.275T>C	p.Leu92Pro	missense	Exon 3 of 4	ENSP00000488117.1	P0C874
	ENSG00000267559	ENST00000585776.5	TSL:2	n.1039+1176A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000455 AC: 4 AN: 87946 Hom.: 0 Cov.: 12

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00138

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: 0.0000623 AC: 5 AN: 80306 AF XY: 0.0000234

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000741

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000371 AC: 31 AN: 836286 Hom.: 0 Cov.: 16 AF XY: 0.0000287 AC XY: 12 AN XY: 417514

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

African (AFR) AF: 0.0000602 AC: 1 AN: 16610

American (AMR) AF: 0.00 AC: 0 AN: 11442

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11560

East Asian (EAS) AF: 0.00210 AC: 27 AN: 12840

South Asian (SAS) AF: 0.00 AC: 0 AN: 59100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1970

European-Non Finnish (NFE) AF: 0.00000150 AC: 1 AN: 665330

Other (OTH) AF: 0.0000651 AC: 2 AN: 30712

⚠️ 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 AF: 0.0000455 AC: 4 AN: 87948 Hom.: 0 Cov.: 12 AF XY: 0.0000498 AC XY: 2 AN XY: 40196

African (AFR) AF: 0.00 AC: 0 AN: 22046

American (AMR) AF: 0.00 AC: 0 AN: 7298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2492

East Asian (EAS) AF: 0.00138 AC: 4 AN: 2890

South Asian (SAS) AF: 0.00 AC: 0 AN: 1960

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 102

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 46962

Other (OTH) AF: 0.00 AC: 0 AN: 1122

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000479 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	0.25
BayesDel_noAF	Benign	-0.90
CADD	Benign	18
DANN	Benign	0.61
DEOGEN2	Benign	0.21	T
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.64	T
MetaRNN	Benign	0.35	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		0.75
PrimateAI	Uncertain	0.53	T
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.71
GERP RS		1.5
Varity_R		0.36
gMVP		0.10
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: rs763508588; hg19: chr9-84560129;