rs149714301

Variant names:

• chr10-100487755-C-G
• rs149714301
• NM_015490.4:c.3401G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-100487755-C-G
• chr10-100487755-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015490.4(SEC31B):​c.3401G>C​(p.Arg1134Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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. R1134Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SEC31B NM_015490.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.496

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39854127).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC31B	NM_015490.4	c.3401G>C	p.Arg1134Pro	missense_variant	Exon 26 of 26	ENST00000370345.8	NP_056305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC31B	ENST00000370345.8	c.3401G>C	p.Arg1134Pro	missense_variant	Exon 26 of 26	1	NM_015490.4	ENSP00000359370.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.0	M
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.27
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.41
MVP		0.52
MPC		0.042
ClinPred		0.98	D
GERP RS		2.0
Varity_R		0.70
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs149714301; hg19: chr10-102247512;