Genetic Variant EMC10:p.Leu107Leu (chr19-50480134-G-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_206538.4(EMC10):c.321G>A(p.Leu107Leu) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L107L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EMC10
NM_206538.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.52

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP7

Synonymous conserved (PhyloP=-1.52 with no splicing effect.

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.321G>A	p.Leu107Leu	synonymous	Exon 4 of 7	NP_996261.1	Q5UCC4-1
	EMC10	NM_175063.6		c.321G>A	p.Leu107Leu	synonymous	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.321G>A	p.Leu107Leu	synonymous	Exon 4 of 7	ENSP00000334037.6	Q5UCC4-1
EMC10	ENST00000376918.7	TSL:1	c.321G>A	p.Leu107Leu	synonymous	Exon 4 of 8	ENSP00000366117.2	Q5UCC4-2
EMC10	ENST00000601780.5	TSL:1	n.*257G>A		non_coding_transcript_exon	Exon 4 of 8	ENSP00000470164.1	M0QYY4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

244836

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1460010

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726094

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44484

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26040

East Asian (EAS)

AF:

0.00

AC:

AN:

39654

South Asian (SAS)

AF:

0.00

AC:

AN:

85622

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53222

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111476

Other (OTH)

AF:

0.00

AC:

AN:

60282

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.9

(source)

DANN

Benign

0.69

PhyloP100

-1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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