Variant 19-50480180-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_206538.4(EMC10):c.367G>A(p.Glu123Lys) 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 1,461,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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

EMC10
NM_206538.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.45

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 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21967274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMC10	NM_206538.4 linkuse as main transcript	c.367G>A	p.Glu123Lys	missense_variant	4/7	ENST00000334976.11	NP_996261.1
EMC10	NM_175063.6 linkuse as main transcript	c.367G>A	p.Glu123Lys	missense_variant	4/8		NP_778233.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMC10	ENST00000334976.11 linkuse as main transcript	c.367G>A	p.Glu123Lys	missense_variant	4/7	1	NM_206538.4	ENSP00000334037	A2	Q5UCC4-1
	ENST00000598194.1 linkuse as main transcript	n.314C>T		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461588

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 12, 2024

The c.367G>A (p.E123K) alteration is located in exon 4 (coding exon 4) of the EMC10 gene. This alteration results from a G to A substitution at nucleotide position 367, causing the glutamic acid (E) at amino acid position 123 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.083

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

.;T;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.034

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.8

L;L;.

MutationTaster

Benign

0.98

D;D

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.71

N;N;.

REVEL

Benign

0.044

Sift

Benign

0.043

D;T;.

Sift4G

Benign

0.074

T;T;T

Polyphen

0.75

P;P;.

Vest4

0.35

MutPred

0.45

Gain of ubiquitination at E123 (P = 0.0101);Gain of ubiquitination at E123 (P = 0.0101);Gain of ubiquitination at E123 (P = 0.0101);

MVP

0.25

MPC

0.35

ClinPred

0.57

GERP RS

2.8

Varity_R

0.068

gMVP

0.42

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over