chr19-50476607-GC-G

Position:

• chr19-50476607-GC-G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_206538.4(EMC10):​c.66del​(p.Ser23ValfsTer82) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EMC10 NM_206538.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.296

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]

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

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.919 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 19-50476607-GC-G is Pathogenic according to our data. Variant chr19-50476607-GC-G is described in ClinVar as [Pathogenic]. Clinvar id is 1704220.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMC10	NM_206538.4	c.66del	p.Ser23ValfsTer82	frameshift_variant	1/7	ENST00000334976.11	NP_996261.1
GARIN5A	NM_001308429.2	c.-220del		5_prime_UTR_variant	1/5	ENST00000600100.6	NP_001295358.1
EMC10	NM_175063.6	c.66del	p.Ser23ValfsTer82	frameshift_variant	1/8		NP_778233.4
GARIN5A	NM_138411.3	c.-220del		5_prime_UTR_variant	1/5		NP_612420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMC10	ENST00000334976.11	c.66del	p.Ser23ValfsTer82	frameshift_variant	1/7	1	NM_206538.4	ENSP00000334037	A2
GARIN5A	ENST00000600100.6	c.-220del		5_prime_UTR_variant	1/5	1	NM_001308429.2	ENSP00000472421	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Neurodevelopmental disorder with dysmorphic facies and variable seizures Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 06, 2022

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr19-50979864;