Variant 19-50480162-G-A 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.349G>A(p.Gly117Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00354 in 1,613,746 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0036 ( 14 hom. )

Consequence

EMC10
NM_206538.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.17

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:

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=0.005236417).

BP6

Variant 19-50480162-G-A is Benign according to our data. Variant chr19-50480162-G-A is described in ClinVar as [Benign]. Clinvar id is 2650342.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00303 (462/152334) while in subpopulation NFE AF= 0.00429 (292/68016). AF 95% confidence interval is 0.00389. There are 0 homozygotes in gnomad4. There are 221 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMC10	NM_206538.4 linkuse as main transcript	c.349G>A	p.Gly117Arg	missense_variant	4/7	ENST00000334976.11	NP_996261.1
EMC10	NM_175063.6 linkuse as main transcript	c.349G>A	p.Gly117Arg	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.349G>A	p.Gly117Arg	missense_variant	4/7	1	NM_206538.4	ENSP00000334037	A2	Q5UCC4-1
	ENST00000598194.1 linkuse as main transcript	n.332C>T		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.00304

AC:

462

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00269

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0117

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00429

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00305

AC:

758

AN:

248780

Hom.:

AF XY:

0.00301

AC XY:

406

AN XY:

134682

show subpopulations

Gnomad AFR exome

AF:

0.000436

Gnomad AMR exome

AF:

0.000320

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00158

Gnomad SAS exome

AF:

0.000197

Gnomad FIN exome

AF:

0.0114

Gnomad NFE exome

AF:

0.00396

Gnomad OTH exome

AF:

0.00331

GnomAD4 exome

AF:

0.00359

AC:

5245

AN:

1461412

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

2556

AN XY:

726960

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00151

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.0107

Gnomad4 NFE exome

AF:

0.00394

Gnomad4 OTH exome

AF:

0.00297

GnomAD4 genome

AF:

0.00303

AC:

462

AN:

152334

Hom.:

Cov.:

AF XY:

0.00297

AC XY:

221

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00270

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0117

Gnomad4 NFE

AF:

0.00429

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00326

Hom.:

Bravo

AF:

0.00223

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00477

AC:

ExAC

AF:

0.00310

AC:

376

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00311

EpiControl

AF:

0.00428

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2024

EMC10: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.046

.;T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.87

D;D;D

MetaRNN

Benign

0.0052

T;T;T

MetaSVM

Benign

-0.71

MutationAssessor

Benign

1.9

L;L;.

MutationTaster

Benign

0.98

D;D

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.93

N;N;.

REVEL

Benign

0.26

Sift

Benign

0.034

D;D;.

Sift4G

Benign

0.11

T;T;T

Polyphen

1.0

D;D;.

Vest4

0.36

MutPred

0.41

Gain of MoRF binding (P = 0.0213);Gain of MoRF binding (P = 0.0213);Gain of MoRF binding (P = 0.0213);

MVP

0.55

MPC

0.68

ClinPred

0.023

GERP RS

2.9

Varity_R

0.074

gMVP

0.64

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