rs2295772

Positions:

• chr10-100505426-G-A

Variant summary

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

The NM_015490.4(SEC31B):​c.1114C>T​(p.Pro372Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,604,228 control chromosomes in the GnomAD database, including 38,038 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 0.21 (3385 hom., cov: 31)
  • Exomes 𝑓: 0.22 (34653 hom.)
• Consequence: SEC31B NM_015490.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.75

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=0.0035551488).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEC31B	NM_015490.4	c.1114C>T	p.Pro372Ser	missense_variant	10/26	ENST00000370345.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEC31B	ENST00000370345.8	c.1114C>T	p.Pro372Ser	missense_variant	10/26	1	NM_015490.4	P1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31458 AN: 151872 Hom.: 3377 Cov.: 31

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.206

GnomAD3 exomes AF: 0.206 AC: 49595 AN: 240672 Hom.: 5388 AF XY: 0.208 AC XY: 26986 AN XY: 129656

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.161

Gnomad ASJ exome AF: 0.198

Gnomad EAS exome AF: 0.142

Gnomad SAS exome AF: 0.226

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.221

Gnomad OTH exome AF: 0.216

GnomAD4 exome AF: 0.216 AC: 313960 AN: 1452238 Hom.: 34653 Cov.: 36 AF XY: 0.217 AC XY: 156693 AN XY: 721820

Gnomad4 AFR exome AF: 0.193

Gnomad4 AMR exome AF: 0.163

Gnomad4 ASJ exome AF: 0.199

Gnomad4 EAS exome AF: 0.177

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.233

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.212

GnomAD4 genome AF: 0.207 AC: 31475 AN: 151990 Hom.: 3385 Cov.: 31 AF XY: 0.208 AC XY: 15444 AN XY: 74294

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.203

Alfa AF: 0.214 Hom.: 1698

Bravo AF: 0.204

TwinsUK AF: 0.216 AC: 802

ALSPAC AF: 0.214 AC: 824

ESP6500AA AF: 0.195 AC: 858

ESP6500EA AF: 0.220 AC: 1893

ExAC AF: 0.208 AC: 25262

Asia WGS AF: 0.192 AC: 666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.3
DANN	Benign	0.81
DEOGEN2	Benign	0.00041	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.024	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.7	N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.32	T
PROVEAN	Benign	2.0	N
REVEL	Benign	0.16
Sift	Benign	1.0	T
Sift4G	Benign	0.82	T
Polyphen		0.0	B
Vest4		0.0050
MPC		0.033
ClinPred		0.0074	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.019
gMVP		0.070

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2295772; hg19: chr10-102265183; COSMIC: COSV64824807; COSMIC: COSV64824807;