Genetic Variant NM_012430.5:c.508G>T (chr3-123225264-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012430.5(SEC22A):c.508G>T(p.Val170Phe) 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. 14/22 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)

Consequence

SEC22A
NM_012430.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.699

Publications

0 publications found

Variant links:

Genes affected

SEC22A (HGNC:20260): (SEC22 homolog A, vesicle trafficking protein) The protein encoded by this gene belongs to the member of the SEC22 family of vesicle trafficking proteins. This protein has similarity to rat SEC22 and may act in the early stages of the secretory pathway. [provided by RefSeq, Nov 2008]

SEC22A links:

PDIA5 (HGNC:24811): (protein disulfide isomerase family A member 5) This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The encoded protein has an N-terminal ER-signal sequence, three catalytically active thioredoxin (TRX) domains, a TRX-like domain, and a C-terminal ER-retention sequence. The N-terminal TRX-like domain is the primary binding site for the major ER chaperone calreticulin and possibly other proteins and substrates as well. Alternative splicing results in multiple protein- and non-protein-coding transcript variants. [provided by RefSeq, Dec 2016]

PDIA5 links:

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ACMG classification

Classification was made for transcript

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=0.13309112).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012430.5. 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
	SEC22A	NM_012430.5	MANE Select	c.508G>T	p.Val170Phe	missense	Exon 4 of 7	NP_036562.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEC22A	ENST00000492595.6	TSL:1 MANE Select	c.508G>T	p.Val170Phe	missense	Exon 4 of 7	ENSP00000417972.1	Q96IW7
SEC22A	ENST00000309934.4	TSL:1	c.508G>T	p.Val170Phe	missense	Exon 3 of 6	ENSP00000310521.4	Q96IW7
SEC22A	ENST00000487572.5	TSL:3	c.508G>T	p.Val170Phe	missense	Exon 5 of 6	ENSP00000420015.1	C9JRY4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.049

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.82

M_CAP

Benign

0.0084

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

0.70

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.2

REVEL

Benign

0.033

Sift

Benign

0.12

Sift4G

Benign

0.11

Polyphen

0.054

Vest4

0.37

MutPred

0.31

Gain of catalytic residue at V170 (P = 0.0535)

MVP

0.20

MPC

0.16

ClinPred

0.40

GERP RS

2.9

Varity_R

0.069

gMVP

0.57

Mutation Taster

=75/25

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over