Genetic Variant EMC6:p.Pro83Ala (chr17-3669393-C-G) – 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_031298.4(EMC6):c.247C>G(p.Pro83Ala) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

EMC6
NM_031298.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.54

Publications

1 publications found

Variant links:

Genes affected

EMC6 (HGNC:28430): (ER membrane protein complex subunit 6) Contributes to membrane insertase activity. Involved in autophagosome assembly; protein insertion into ER membrane by stop-transfer membrane-anchor sequence; and tail-anchored membrane protein insertion into ER membrane. Is integral component of endoplasmic reticulum membrane and integral component of omegasome membrane. Part of EMC complex. [provided by Alliance of Genome Resources, Apr 2022]

EMC6 links:

P2RX5-TAX1BP3 (HGNC:49191): (P2RX5-TAX1BP3 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring P2RX5 (purinergic receptor P2X, ligand-gated ion channel, 5) and TAX1BP3 (Tax1 binding protein 3) genes on chromosome 17. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

P2RX5-TAX1BP3 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=0.16772717).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031298.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EMC6	NM_031298.4	MANE Select	c.247C>G	p.Pro83Ala	missense	Exon 2 of 2	NP_112588.1	Q9BV81
EMC6	NM_001014764.3		c.247C>G	p.Pro83Ala	missense	Exon 2 of 2	NP_001014764.1	Q9BV81
P2RX5-TAX1BP3	NR_037928.1		n.4759G>C		non_coding_transcript_exon	Exon 12 of 15

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EMC6	ENST00000248378.6	TSL:1 MANE Select	c.247C>G	p.Pro83Ala	missense	Exon 2 of 2	ENSP00000248378.4	Q9BV81
P2RX5-TAX1BP3	ENST00000550383.1	TSL:2	n.*3061G>C		non_coding_transcript_exon	Exon 12 of 15	ENSP00000455681.1
P2RX5-TAX1BP3	ENST00000550383.1	TSL:2	n.*3061G>C		3_prime_UTR	Exon 12 of 15	ENSP00000455681.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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

0.069

BayesDel_addAF

Benign

-0.025

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.013

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.085

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0023

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

PhyloP100

3.5

PrimateAI

Uncertain

0.66

PROVEAN

Benign

0.84

REVEL

Benign

0.13

Sift

Benign

0.82

Sift4G

Benign

0.78

Polyphen

0.0020

Vest4

0.46

MutPred

0.28

Gain of helix (P = 0.0325)

MVP

0.11

MPC

1.1

ClinPred

0.72

GERP RS

5.1

Varity_R

0.24

gMVP

0.71

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

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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