19-50480134-G-T

Variant names:

• chr19-50480134-G-T
• rs748954464
• NM_206538.4:c.321G>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS1

The NM_206538.4(EMC10):​c.321G>T​(p.Leu107Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,612,236 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000049 (1 hom.)
• Consequence: EMC10 NM_206538.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.52
• 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

ENSG00000268854 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 19-50480134-G-T is Benign according to our data. Variant chr19-50480134-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2650341.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.52 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.0000486 (71/1460010) while in subpopulation SAS AF = 0.000794 (68/85622). AF 95% confidence interval is 0.000642. There are 1 homozygotes in GnomAdExome4. There are 54 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

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

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000613 AC: 15 AN: 244836 AF XY: 0.0000678

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: 0.00000904

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000486 AC: 71 AN: 1460010 Hom.: 1 Cov.: 31 AF XY: 0.0000744 AC XY: 54 AN XY: 726094

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26040

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.000794 AC: 68 AN: 85622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53222

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111476

Other (OTH) AF: 0.0000166 AC: 1 AN: 60282

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152226 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74362

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	7.1
DANN	Benign	0.67
PhyloP100		-1.5

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

Other links and lift over

dbSNP: rs748954464; hg19: chr19-50983391;