NM_001145197.1:c.2496C>A

Variant names:

• chr9-81932657-C-A
• rs781376500
• NM_001145197.1:c.2496C>A

Variant summary

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

The NM_001145197.1(SPATA31D4):​c.2496C>A​(p.Ser832Arg) 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 0.00047 (1 hom., cov: 20)
  • Exomes 𝑓: 0.000047 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPATA31D4 NM_001145197.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0660
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15085861).

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.2496C>A	p.Ser832Arg	missense	Exon 4 of 4	NP_001138669.1	Q6ZUB0
	LOC105376105	NR_188610.1		n.1040-1263G>T		intron	N/A
	LOC105376105	NR_188611.1		n.1229-1263G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31D4	ENST00000419782.5	TSL:1 MANE Select	c.2496C>A	p.Ser832Arg	missense	Exon 4 of 4	ENSP00000488251.1	Q6ZUB0
	ENSG00000267559	ENST00000585776.5	TSL:2	n.1040-1263G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000444 AC: 59 AN: 132924 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00151

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000227

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: 0.00112

GnomAD2 exomes AF: 0.0000662 AC: 12 AN: 181172 AF XY: 0.0000721

Gnomad AFR exome AF: 0.00117

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000475 AC: 66 AN: 1390266 Hom.: 1 Cov.: 30 AF XY: 0.0000448 AC XY: 31 AN XY: 691290

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

African (AFR) AF: 0.00161 AC: 52 AN: 32218

American (AMR) AF: 0.0000475 AC: 2 AN: 42078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25274

East Asian (EAS) AF: 0.00 AC: 0 AN: 38960

South Asian (SAS) AF: 0.00 AC: 0 AN: 83808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50772

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5238

European-Non Finnish (NFE) AF: 0.00000285 AC: 3 AN: 1054214

Other (OTH) AF: 0.000156 AC: 9 AN: 57704

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000456988), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000466 AC: 62 AN: 133024 Hom.: 1 Cov.: 20 AF XY: 0.000403 AC XY: 26 AN XY: 64476

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

African (AFR) AF: 0.00159 AC: 57 AN: 35936

American (AMR) AF: 0.000227 AC: 3 AN: 13210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3180

East Asian (EAS) AF: 0.00 AC: 0 AN: 4724

South Asian (SAS) AF: 0.00 AC: 0 AN: 4278

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8728

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 258

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 60122

Other (OTH) AF: 0.00111 AC: 2 AN: 1800

⚠️ 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: 0.000759 Hom.: 0

ExAC AF: 0.0000265 AC: 3

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	Uncertain	0.37
BayesDel_noAF	Benign	-0.94
CADD	Benign	13
DANN	Benign	0.68
DEOGEN2	Benign	0.020	T
FATHMM_MKL	Benign	0.0033	N
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.15	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		-0.066
PrimateAI	Uncertain	0.52	T
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.32
GERP RS		-0.29
Varity_R		0.069
gMVP		0.077
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: rs781376500; hg19: chr9-84547572;