Variant 19-50476651-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_206538.4(EMC10):c.107C>G(p.Ala36Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000548 in 1,528,610 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 6 hom. )

Consequence

EMC10
NM_206538.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.288

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:

GARIN5A (HGNC:25107): (golgi associated RAB2 interactor 5A)

GARIN5A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006118983).

BP6

Variant 19-50476651-C-G is Benign according to our data. Variant chr19-50476651-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3025286.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00294 (448/152308) while in subpopulation AFR AF= 0.0103 (429/41580). AF 95% confidence interval is 0.00951. There are 1 homozygotes in gnomad4. There are 227 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMC10	NM_206538.4 link	c.107C>G	p.Ala36Gly	missense_variant	1/7	ENST00000334976.11	NP_996261.1	Q5UCC4-1
GARIN5A	NM_001308429.2 link	c.-263G>C		5_prime_UTR_variant	1/5	ENST00000600100.6	NP_001295358.1	Q6IPT2-1
EMC10	NM_175063.6 link	c.107C>G	p.Ala36Gly	missense_variant	1/8		NP_778233.4	Q5UCC4-2
GARIN5A	NM_138411.3 link	c.-263G>C		5_prime_UTR_variant	1/5		NP_612420.1	Q6IPT2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMC10	ENST00000334976.11 link	c.107C>G	p.Ala36Gly	missense_variant	1/7	1	NM_206538.4	ENSP00000334037.6		Q5UCC4-1
GARIN5A	ENST00000600100.6 link	c.-263G>C		5_prime_UTR_variant	1/5	1	NM_001308429.2	ENSP00000472421.2		Q6IPT2-1

Frequencies

GnomAD3 genomes

AF:

0.00294

AC:

447

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0103

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000652

AC:

AN:

139504

Hom.:

AF XY:

0.000594

AC XY:

AN XY:

77422

show subpopulations

Gnomad AFR exome

AF:

0.0122

Gnomad AMR exome

AF:

0.000258

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000499

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000283

AC:

390

AN:

1376302

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

174

AN XY:

679228

show subpopulations

Gnomad4 AFR exome

AF:

0.0104

Gnomad4 AMR exome

AF:

0.000315

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:

0.0000316

Gnomad4 OTH exome

AF:

0.000473

GnomAD4 genome

AF:

0.00294

AC:

448

AN:

152308

Hom.:

Cov.:

AF XY:

0.00305

AC XY:

227

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0103

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000170

Hom.:

Bravo

AF:

0.00333

ESP6500AA

AF:

0.00709

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000595

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

EMC10: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.016

.;T;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.73

T;T;T

MetaRNN

Benign

0.0061

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N;.

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.86

N;N;.

REVEL

Benign

0.062

Sift

Benign

0.11

T;T;.

Sift4G

Uncertain

0.037

D;D;D

Polyphen

0.065

B;B;.

Vest4

0.22

MVP

0.085

MPC

0.14

ClinPred

0.022

GERP RS

-2.9

Varity_R

0.057

gMVP

0.23

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over