9-81932404-G-T

Variant names:

• chr9-81932404-G-T
• rs1823768562
• NM_001145197.1:c.2243G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145197.1(SPATA31D4):​c.2243G>T​(p.Ser748Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 0.000011 (0 hom., cov: 12)
  • Failed GnomAD Quality Control
• Consequence: SPATA31D4 NM_001145197.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.140

Genes affected

SPATA31D4 (HGNC:38601): (SPATA31 subfamily D member 4) 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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07282084).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31D4	NM_001145197.1	c.2243G>T	p.Ser748Ile	missense_variant	Exon 4 of 4	ENST00000419782.5	NP_001138669.1
LOC105376105	NR_188610.1	n.1040-1010C>A		intron_variant	Intron 4 of 5
LOC105376105	NR_188611.1	n.1229-1010C>A		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA31D4	ENST00000419782.5	c.2243G>T	p.Ser748Ile	missense_variant	Exon 4 of 4	1	NM_001145197.1	ENSP00000488251.1
ENSG00000267559	ENST00000585776.5	n.1040-1010C>A		intron_variant	Intron 4 of 4	2

Frequencies

GnomAD3 genomes AF: 0.0000112 AC: 1 AN: 89600 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: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000231

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 27

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000112 AC: 1 AN: 89600 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 42382

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: 0.0000231

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

Oct 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2243G>T (p.S748I) alteration is located in exon 4 (coding exon 4) of the SPATA31D4 gene. This alteration results from a G to T substitution at nucleotide position 2243, causing the serine (S) at amino acid position 748 to be replaced by an isoleucine (I). 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	0.098
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.14
DANN	Benign	0.22
DEOGEN2	Benign	0.016	T
FATHMM_MKL	Benign	0.0049	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.073	T
MutationAssessor	Benign	2.0	M
PrimateAI	Benign	0.38	T
Sift4G	Benign	0.094	T
Polyphen		0.11	B
Vest4		0.065
GERP RS		-0.39
Varity_R		0.12
gMVP		0.087

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1823768562; hg19: chr9-84547319;