chr19-50479052-C-G

Variant names:

• chr19-50479052-C-G
• rs764238587
• NM_206538.4:c.283C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_206538.4(EMC10):​c.283C>G​(p.Arg95Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,453,752 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R95W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EMC10 NM_206538.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.66
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.283C>G	p.Arg95Gly	missense	Exon 3 of 7	NP_996261.1	Q5UCC4-1
	EMC10	NM_175063.6		c.283C>G	p.Arg95Gly	missense	Exon 3 of 8	NP_778233.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMC10	ENST00000334976.11	TSL:1 MANE Select	c.283C>G	p.Arg95Gly	missense	Exon 3 of 7	ENSP00000334037.6	Q5UCC4-1
	EMC10	ENST00000376918.7	TSL:1	c.283C>G	p.Arg95Gly	missense	Exon 3 of 8	ENSP00000366117.2	Q5UCC4-2
	EMC10	ENST00000601780.5	TSL:1	n.*219C>G		non_coding_transcript_exon	Exon 3 of 8	ENSP00000470164.1	M0QYY4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453752 Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2 AN XY: 722628

African (AFR) AF: 0.00 AC: 0 AN: 33296

American (AMR) AF: 0.00 AC: 0 AN: 43948

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26028

East Asian (EAS) AF: 0.00 AC: 0 AN: 39356

South Asian (SAS) AF: 0.00 AC: 0 AN: 84924

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52732

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4160

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109338

Other (OTH) AF: 0.00 AC: 0 AN: 59970

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.070	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.7
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.21
Sift	Benign	0.059	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.65
MutPred		0.48		Gain of relative solvent accessibility (P = 0.0275)
MVP		0.52
MPC		0.71
ClinPred		0.98	D
GERP RS		3.9
Varity_R		0.45
gMVP		0.70
Mutation Taster		=29/71	disease causing

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

Other links and lift over

dbSNP: rs764238587; hg19: chr19-50982309;