rs2295772

Variant names:

• chr10-100505426-G-A
• rs2295772
• NM_015490.4:c.1114C>T
• SEC31B p.Pro372Ser

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 29 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]

ENSG00000255339 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.1114C>T	p.Pro372Ser	missense	Exon 10 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.1114C>T	p.Pro372Ser	missense	Exon 10 of 26	ENSP00000359370.3	Q9NQW1-1
	SEC31B	ENST00000479697.5	TSL:1	n.*1204C>T		non_coding_transcript_exon	Exon 8 of 26	ENSP00000473995.1	F6TTE0
	SEC31B	ENST00000479697.5	TSL:1	n.*1204C>T		3_prime_UTR	Exon 8 of 26	ENSP00000473995.1	F6TTE0

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

GnomAD2 exomes AF: 0.206 AC: 49595 AN: 240672 AF XY: 0.208

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 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

African (AFR) AF: 0.193 AC: 6421 AN: 33212

American (AMR) AF: 0.163 AC: 7153 AN: 44006

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 5071 AN: 25472

East Asian (EAS) AF: 0.177 AC: 6999 AN: 39432

South Asian (SAS) AF: 0.228 AC: 19211 AN: 84212

European-Finnish (FIN) AF: 0.233 AC: 12309 AN: 52890

Middle Eastern (MID) AF: 0.217 AC: 1240 AN: 5726

European-Non Finnish (NFE) AF: 0.219 AC: 242827 AN: 1107226

Other (OTH) AF: 0.212 AC: 12729 AN: 60062

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

African (AFR) AF: 0.202 AC: 8368 AN: 41444

American (AMR) AF: 0.180 AC: 2751 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 677 AN: 3466

East Asian (EAS) AF: 0.144 AC: 744 AN: 5184

South Asian (SAS) AF: 0.230 AC: 1104 AN: 4810

European-Finnish (FIN) AF: 0.221 AC: 2336 AN: 10564

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14814 AN: 67942

Other (OTH) AF: 0.203 AC: 429 AN: 2110

Alfa AF: 0.212 Hom.: 2721

Bravo AF: 0.204

Asia WGS AF: 0.192 AC: 666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		2.8
PrimateAI	Benign	0.32	T
PROVEAN	Benign	2.0	N
REVEL	Benign	0.16
Sift	Benign	1.0	T
Sift4G	Benign	0.82	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.019
gMVP		0.070
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2295772;

hg19: chr10-102265183;

COSMIC: COSV64824807;

COSMIC: COSV64824807;