rs2298075

Variant names:

• chr10-100487651-C-A
• rs2298075
• NM_015490.4:c.3505G>T

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A1169V) has been classified as Uncertain significance.

• 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
• Publications: 37 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015490.4. 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
	SEC31B	NM_015490.4	MANE Select	c.3505G>T	p.Ala1169Ser	missense	Exon 26 of 26	NP_056305.1	Q9NQW1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEC31B	ENST00000370345.8	TSL:1 MANE Select	c.3505G>T	p.Ala1169Ser	missense	Exon 26 of 26	ENSP00000359370.3	Q9NQW1-1
	SEC31B	ENST00000479697.5	TSL:1	n.*3702G>T		non_coding_transcript_exon	Exon 26 of 26	ENSP00000473995.1	F6TTE0
	SEC31B	ENST00000479697.5	TSL:1	n.*3702G>T		3_prime_UTR	Exon 26 of 26	ENSP00000473995.1	F6TTE0

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

GnomAD2 exomes AF: 0.208 AC: 51577 AN: 248484 AF XY: 0.210

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 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

African (AFR) AF: 0.210 AC: 7028 AN: 33464

American (AMR) AF: 0.161 AC: 7199 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 5418 AN: 26114

East Asian (EAS) AF: 0.156 AC: 6190 AN: 39680

South Asian (SAS) AF: 0.231 AC: 19830 AN: 85992

European-Finnish (FIN) AF: 0.234 AC: 12440 AN: 53192

Middle Eastern (MID) AF: 0.213 AC: 1230 AN: 5764

European-Non Finnish (NFE) AF: 0.227 AC: 251850 AN: 1111282

Other (OTH) AF: 0.219 AC: 13233 AN: 60324

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

African (AFR) AF: 0.215 AC: 8916 AN: 41498

American (AMR) AF: 0.184 AC: 2809 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 707 AN: 3470

East Asian (EAS) AF: 0.129 AC: 669 AN: 5176

South Asian (SAS) AF: 0.231 AC: 1115 AN: 4824

European-Finnish (FIN) AF: 0.223 AC: 2356 AN: 10584

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15424 AN: 68012

Other (OTH) AF: 0.204 AC: 431 AN: 2114

Alfa AF: 0.221 Hom.: 12437

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 v4.9

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
PhyloP100		3.4
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
Mutation Taster		=94/6	polymorphism (auto)

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