9-81947433-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_207416.3(SPATA31D3):​c.2180G>T​(p.Gly727Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 10)
  • Failed GnomAD Quality Control
• Consequence: SPATA31D3 NM_207416.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.708

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17511001).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31D3	NM_207416.3	c.2180G>T	p.Gly727Val	missense_variant	Exon 4 of 4	ENST00000445385.3	NP_997299.2
LOC105376105	NR_188610.1	n.943-947C>A		intron_variant	Intron 3 of 5
LOC105376105	NR_188611.1	n.943-947C>A		intron_variant	Intron 3 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA31D3	ENST00000445385.3	c.2180G>T	p.Gly727Val	missense_variant	Exon 4 of 4	1	NM_207416.3	ENSP00000488117.1
ENSG00000267559	ENST00000585776.5	n.943-947C>A		intron_variant	Intron 3 of 4	2
ENSG00000267559	ENST00000592744.1	n.519-947C>A		intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 81518 Hom.: 0 Cov.: 10 FAILED QC

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 17

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 81518 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 38036

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 18, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2180G>T (p.G727V) alteration is located in exon 4 (coding exon 4) of the SPATA31D3 gene. This alteration results from a G to T substitution at nucleotide position 2180, causing the glycine (G) at amino acid position 727 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.4
DANN	Benign	0.50
DEOGEN2	Benign	0.060	T
FATHMM_MKL	Benign	0.0056	N
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.18	T
MutationAssessor	Uncertain	2.9	M
PrimateAI	Benign	0.41	T
Sift4G	Uncertain	0.032	D
Polyphen		0.95	P
Vest4		0.063
GERP RS		0.26
Varity_R		0.042
gMVP		0.050

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-84562348;