chr10-100506090-A-C

Variant names:

• chr10-100506090-A-C
• rs2295774
• NM_015490.4:c.994T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015490.4(SEC31B):​c.994T>G​(p.Ser332Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,614,028 control chromosomes in the GnomAD database, including 36,687 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.17 (2606 hom., cov: 32)
  • Exomes 𝑓: 0.21 (34081 hom.)
• Consequence: SEC31B NM_015490.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.43

Genes affected

SEC31B (HGNC:23197): (SEC31 homolog B, COPII coat complex component) This gene encodes a protein of unknown function. The protein has moderate similarity to rat VAP1 protein which is an endosomal membrane-associated protein, containing a putative Ca2+/calmodulin-dependent kinase II phosphorylation site. [provided by RefSeq, Jul 2008]

ENSG00000255339 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018028915).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC31B	NM_015490.4	c.994T>G	p.Ser332Ala	missense_variant	Exon 9 of 26	ENST00000370345.8	NP_056305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC31B	ENST00000370345.8	c.994T>G	p.Ser332Ala	missense_variant	Exon 9 of 26	1	NM_015490.4	ENSP00000359370.3

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26461 AN: 152072 Hom.: 2604 Cov.: 32

Gnomad AFR AF: 0.0864

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.183

GnomAD3 exomes AF: 0.197 AC: 49510 AN: 251288 Hom.: 5247 AF XY: 0.201 AC XY: 27349 AN XY: 135804

Gnomad AFR exome AF: 0.0850

Gnomad AMR exome AF: 0.154

Gnomad ASJ exome AF: 0.195

Gnomad EAS exome AF: 0.143

Gnomad SAS exome AF: 0.223

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.220

Gnomad OTH exome AF: 0.209

GnomAD4 exome AF: 0.213 AC: 311056 AN: 1461838 Hom.: 34081 Cov.: 37 AF XY: 0.214 AC XY: 155775 AN XY: 727230

Gnomad4 AFR exome AF: 0.0783

Gnomad4 AMR exome AF: 0.155

Gnomad4 ASJ exome AF: 0.199

Gnomad4 EAS exome AF: 0.178

Gnomad4 SAS exome AF: 0.227

Gnomad4 FIN exome AF: 0.233

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.204

GnomAD4 genome AF: 0.174 AC: 26456 AN: 152190 Hom.: 2606 Cov.: 32 AF XY: 0.176 AC XY: 13083 AN XY: 74402

Gnomad4 AFR AF: 0.0863

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.181

Alfa AF: 0.203 Hom.: 6076

Bravo AF: 0.166

TwinsUK AF: 0.217 AC: 804

ALSPAC AF: 0.214 AC: 826

ESP6500AA AF: 0.0772 AC: 340

ESP6500EA AF: 0.220 AC: 1888

ExAC AF: 0.198 AC: 24034

Asia WGS AF: 0.186 AC: 646 AN: 3478

EpiCase AF: 0.208

EpiControl AF: 0.210

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.080	T
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	M
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.37
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.29
MPC		0.21
ClinPred		0.045	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.59
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs2295774; hg19: chr10-102265847; COSMIC: COSV64824800; COSMIC: COSV64824800;