NM_001145197.1:c.2243G>T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145197.1. 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
	SPATA31D4	NM_001145197.1	MANE Select	c.2243G>T	p.Ser748Ile	missense	Exon 4 of 4	NP_001138669.1	Q6ZUB0
	LOC105376105	NR_188610.1		n.1040-1010C>A		intron	N/A
	LOC105376105	NR_188611.1		n.1229-1010C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31D4	ENST00000419782.5	TSL:1 MANE Select	c.2243G>T	p.Ser748Ile	missense	Exon 4 of 4	ENSP00000488251.1	Q6ZUB0
	ENSG00000267559	ENST00000585776.5	TSL:2	n.1040-1010C>A		intron	N/A

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

⚠️ 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: 22958

American (AMR) AF: 0.00 AC: 0 AN: 8042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2514

East Asian (EAS) AF: 0.00 AC: 0 AN: 3698

South Asian (SAS) AF: 0.00 AC: 0 AN: 2774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 172

European-Non Finnish (NFE) AF: 0.0000231 AC: 1 AN: 43218

Other (OTH) AF: 0.00 AC: 0 AN: 1164

⚠️ 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

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	0.098
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
PhyloP100		-0.14
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
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1823768562; hg19: chr9-84547319;