dbSNP rs2049973575: EMC6:p.Arg8Gln (chr17-3669169-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_031298.4(EMC6):c.23G>A(p.Arg8Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. R8L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EMC6
NM_031298.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.09

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39359748).

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.23G>A	p.Arg8Gln	missense	Exon 2 of 2	NP_112588.1	Q9BV81
EMC6	NM_001014764.3		c.23G>A	p.Arg8Gln	missense	Exon 2 of 2	NP_001014764.1	Q9BV81
P2RX5-TAX1BP3	NR_037928.1		n.4983C>T		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.23G>A	p.Arg8Gln	missense	Exon 2 of 2	ENSP00000248378.4	Q9BV81
P2RX5-TAX1BP3	ENST00000550383.1	TSL:2	n.*3285C>T		non_coding_transcript_exon	Exon 12 of 15	ENSP00000455681.1
P2RX5-TAX1BP3	ENST00000550383.1	TSL:2	n.*3285C>T		3_prime_UTR	Exon 12 of 15	ENSP00000455681.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1394916

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

687836

African (AFR)

AF:

0.00

AC:

AN:

32140

American (AMR)

AF:

0.00

AC:

AN:

36964

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25050

East Asian (EAS)

AF:

0.00

AC:

AN:

36820

South Asian (SAS)

AF:

0.00

AC:

AN:

81152

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5472

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078062

Other (OTH)

AF:

0.00

AC:

AN:

57844

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.0098

MetaRNN

Benign

0.39

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

7.1

PrimateAI

Uncertain

0.76

PROVEAN

Benign

0.41

REVEL

Benign

0.18

Sift

Benign

0.32

Sift4G

Benign

0.40

Polyphen

0.58

Vest4

0.76

MutPred

0.53

Gain of catalytic residue at R8 (P = 0.0519)

MVP

0.18

MPC

1.4

ClinPred

0.91

GERP RS

5.3

PromoterAI

0.18

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.80

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