rs2298075

Positions:

• chr10-100487651-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.3505G>T​(p.Ala1169Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,612,572 control chromosomes in the GnomAD database, including 40,335 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.21 (3605 hom., cov: 32)
  • Exomes 𝑓: 0.22 (36730 hom.)
• Consequence: SEC31B NM_015490.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.43

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0021184087).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEC31B	NM_015490.4	c.3505G>T	p.Ala1169Ser	missense_variant	26/26	ENST00000370345.8	NP_056305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEC31B	ENST00000370345.8	c.3505G>T	p.Ala1169Ser	missense_variant	26/26	1	NM_015490.4	ENSP00000359370.3

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32638 AN: 152060 Hom.: 3589 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.207

GnomAD3 exomes AF: 0.208 AC: 51577 AN: 248484 Hom.: 5572 AF XY: 0.210 AC XY: 28172 AN XY: 134340

Gnomad AFR exome AF: 0.209

Gnomad AMR exome AF: 0.159

Gnomad ASJ exome AF: 0.201

Gnomad EAS exome AF: 0.126

Gnomad SAS exome AF: 0.226

Gnomad FIN exome AF: 0.235

Gnomad NFE exome AF: 0.225

Gnomad OTH exome AF: 0.214

GnomAD4 exome AF: 0.222 AC: 324418 AN: 1460394 Hom.: 36730 Cov.: 34 AF XY: 0.223 AC XY: 162112 AN XY: 726366

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.207

Gnomad4 EAS exome AF: 0.156

Gnomad4 SAS exome AF: 0.231

Gnomad4 FIN exome AF: 0.234

Gnomad4 NFE exome AF: 0.227

Gnomad4 OTH exome AF: 0.219

GnomAD4 genome AF: 0.215 AC: 32677 AN: 152178 Hom.: 3605 Cov.: 32 AF XY: 0.214 AC XY: 15937 AN XY: 74386

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.204

Alfa AF: 0.222 Hom.: 9642

Bravo AF: 0.212

TwinsUK AF: 0.224 AC: 831

ALSPAC AF: 0.220 AC: 846

ESP6500AA AF: 0.206 AC: 908

ESP6500EA AF: 0.227 AC: 1955

ExAC AF: 0.211 AC: 25620

Asia WGS AF: 0.193 AC: 669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.0061	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.48
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.77	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.075
Sift	Benign	0.22	T
Sift4G	Benign	0.19	T
Polyphen		0.012	B
Vest4		0.020
MPC		0.032
ClinPred		0.0080	T
GERP RS		1.2
Varity_R		0.031
gMVP		0.15

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

Publications

LitVar

Other links and lift over

dbSNP: rs2298075; hg19: chr10-102247408; COSMIC: COSV59325470; COSMIC: COSV59325470;