10-100509328-C-A

Position:

• chr10-100509328-C-A

Variant summary

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

The NM_015490.4(SEC31B):​c.387G>T​(p.Leu129Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,612,694 control chromosomes in the GnomAD database, including 39,189 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.22 (3841 hom., cov: 32)
  • Exomes 𝑓: 0.22 (35348 hom.)
• Consequence: SEC31B NM_015490.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.753

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019181669).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC31B	NM_015490.4	c.387G>T	p.Leu129Phe	missense_variant	4/26	ENST00000370345.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC31B	ENST00000370345.8	c.387G>T	p.Leu129Phe	missense_variant	4/26	1	NM_015490.4	P1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33487 AN: 151882 Hom.: 3830 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.218

GnomAD3 exomes AF: 0.209 AC: 52421 AN: 250440 Hom.: 5754 AF XY: 0.210 AC XY: 28487 AN XY: 135406

Gnomad AFR exome AF: 0.246

Gnomad AMR exome AF: 0.164

Gnomad ASJ exome AF: 0.195

Gnomad EAS exome AF: 0.143

Gnomad SAS exome AF: 0.225

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.220

Gnomad OTH exome AF: 0.217

GnomAD4 exome AF: 0.218 AC: 318153 AN: 1460694 Hom.: 35348 Cov.: 32 AF XY: 0.219 AC XY: 158796 AN XY: 726664

Gnomad4 AFR exome AF: 0.238

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.199

Gnomad4 EAS exome AF: 0.178

Gnomad4 SAS exome AF: 0.229

Gnomad4 FIN exome AF: 0.233

Gnomad4 NFE exome AF: 0.220

Gnomad4 OTH exome AF: 0.216

GnomAD4 genome AF: 0.220 AC: 33512 AN: 152000 Hom.: 3841 Cov.: 32 AF XY: 0.221 AC XY: 16418 AN XY: 74312

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.215

Alfa AF: 0.217 Hom.: 9538

Bravo AF: 0.220

TwinsUK AF: 0.217 AC: 805

ALSPAC AF: 0.214 AC: 826

ESP6500AA AF: 0.240 AC: 1058

ESP6500EA AF: 0.221 AC: 1899

ExAC AF: 0.213 AC: 25868

Asia WGS AF: 0.195 AC: 677 AN: 3478

EpiCase AF: 0.209

EpiControl AF: 0.211

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Benign	0.91
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.3	N
MutationTaster	Benign	3.9e-20	P;P;P;P;P
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.041
MutPred		0.26		Gain of catalytic residue at L129 (P = 0.0456);
MPC		0.035
ClinPred		0.010	T
GERP RS		4.8
Varity_R		0.074
gMVP		0.29

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: rs3793706; hg19: chr10-102269085; COSMIC: COSV100944804; COSMIC: COSV100944804;