Genetic Variant EMC10:p.Gly121Ala (chr19-50480175-G-C) – 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_206538.4(EMC10):c.362G>C(p.Gly121Ala) 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

EMC10
NM_206538.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.835

Publications

0 publications found

Variant links:

Genes affected

EMC10 (HGNC:27609): (ER membrane protein complex subunit 10) Contributes to membrane insertase activity. Involved in positive regulation of angiogenesis; positive regulation of endothelial cell proliferation; and protein insertion into ER membrane. Located in extracellular region. Is integral component of endoplasmic reticulum membrane. Part of EMC complex. [provided by Alliance of Genome Resources, Apr 2022]

EMC10 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with dysmorphic facies and variable seizures
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
neurodevelopmental disorder
Inheritance: AR Classification: STRONG Submitted by: G2P
global developmental delay with or without impaired intellectual development
Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

EMC10 links:

ENSG00000268854 (HGNC:):

ENSG00000268854 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=0.15058261).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206538.4. 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
	EMC10	NM_206538.4	MANE Select	c.362G>C	p.Gly121Ala	missense	Exon 4 of 7	NP_996261.1	Q5UCC4-1
	EMC10	NM_175063.6		c.362G>C	p.Gly121Ala	missense	Exon 4 of 8	NP_778233.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EMC10	ENST00000334976.11	TSL:1 MANE Select	c.362G>C	p.Gly121Ala	missense	Exon 4 of 7	ENSP00000334037.6	Q5UCC4-1
EMC10	ENST00000376918.7	TSL:1	c.362G>C	p.Gly121Ala	missense	Exon 4 of 8	ENSP00000366117.2	Q5UCC4-2
EMC10	ENST00000601780.5	TSL:1	n.*298G>C		non_coding_transcript_exon	Exon 4 of 8	ENSP00000470164.1	M0QYY4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.011

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.83

M_CAP

Benign

0.0070

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.98

MutationAssessor

Benign

2.0

PhyloP100

0.83

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.60

REVEL

Benign

0.13

Sift

Benign

0.19

Sift4G

Benign

0.22

Polyphen

0.73

Vest4

0.26

MutPred

0.35

Loss of loop (P = 0.0112)

MVP

0.30

MPC

0.27

ClinPred

0.17

GERP RS

3.9

Varity_R

0.039

gMVP

0.41

Mutation Taster

=90/10

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

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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