chr10-100487639-T-C

Variant names:

• chr10-100487639-T-C
• NM_015490.4:c.3517A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015490.4(SEC31B):​c.3517A>G​(p.Ile1173Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SEC31B NM_015490.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.49
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16804284).

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.3517A>G	p.Ile1173Val	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.3517A>G	p.Ile1173Val	missense	Exon 26 of 26	ENSP00000359370.3	Q9NQW1-1
	SEC31B	ENST00000479697.5	TSL:1	n.*3714A>G		non_coding_transcript_exon	Exon 26 of 26	ENSP00000473995.1	F6TTE0
	SEC31B	ENST00000479697.5	TSL:1	n.*3714A>G		3_prime_UTR	Exon 26 of 26	ENSP00000473995.1	F6TTE0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461006 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726698

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86044

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111676

Other (OTH) AF: 0.00 AC: 0 AN: 60364

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.57
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.5
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.15
Sift	Benign	0.90	T
Sift4G	Benign	0.94	T
Polyphen		0.20	B
Vest4		0.26
MutPred		0.33		Loss of catalytic residue at L1178 (P = 0.0426)
MVP		0.37
MPC		0.033
ClinPred		0.23	T
GERP RS		4.7
Varity_R		0.025
gMVP		0.095
Mutation Taster		=77/23	polymorphism

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

hg19: chr10-102247396;