19-50476539-G-C

Variant names:

• chr19-50476539-G-C
• rs150737582
• NM_206538.4:c.-6G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_206538.4(EMC10):​c.-6G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000501 in 1,571,494 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (3 hom.)
• Consequence: EMC10 NM_206538.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.248
• Publications: 1 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]

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 19-50476539-G-C is Benign according to our data. Variant chr19-50476539-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2650339.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00272 (414/152370) while in subpopulation AFR AF = 0.00947 (394/41596). AF 95% confidence interval is 0.0087. There are 3 homozygotes in GnomAd4. There are 195 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.-6G>C		5_prime_UTR	Exon 1 of 7	NP_996261.1	Q5UCC4-1
	GARIN5A	NM_001308429.2	MANE Select	c.-151C>G		5_prime_UTR	Exon 1 of 5	NP_001295358.1	Q6IPT2-1
	EMC10	NM_175063.6		c.-6G>C		5_prime_UTR	Exon 1 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.-6G>C		5_prime_UTR	Exon 1 of 7	ENSP00000334037.6	Q5UCC4-1
	GARIN5A	ENST00000600100.6	TSL:1 MANE Select	c.-151C>G		5_prime_UTR	Exon 1 of 5	ENSP00000472421.2	Q6IPT2-1
	EMC10	ENST00000376918.7	TSL:1	c.-6G>C		5_prime_UTR	Exon 1 of 8	ENSP00000366117.2	Q5UCC4-2

Frequencies

GnomAD3 genomes AF: 0.00272 AC: 414 AN: 152252 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00950

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.000734 AC: 131 AN: 178394 AF XY: 0.000544

Gnomad AFR exome AF: 0.0118

Gnomad AMR exome AF: 0.000573

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000134

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000263 AC: 373 AN: 1419124 Hom.: 3 Cov.: 32 AF XY: 0.000241 AC XY: 170 AN XY: 704282

African (AFR) AF: 0.00911 AC: 295 AN: 32386

American (AMR) AF: 0.000538 AC: 22 AN: 40858

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25514

East Asian (EAS) AF: 0.00 AC: 0 AN: 37410

South Asian (SAS) AF: 0.00 AC: 0 AN: 83034

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40878

Middle Eastern (MID) AF: 0.000729 AC: 3 AN: 4116

European-Non Finnish (NFE) AF: 0.00000274 AC: 3 AN: 1096142

Other (OTH) AF: 0.000851 AC: 50 AN: 58786

GnomAD4 genome AF: 0.00272 AC: 414 AN: 152370 Hom.: 3 Cov.: 32 AF XY: 0.00262 AC XY: 195 AN XY: 74512

African (AFR) AF: 0.00947 AC: 394 AN: 41596

American (AMR) AF: 0.000653 AC: 10 AN: 15310

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68032

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.000131 Hom.: 0

Bravo AF: 0.00310

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	-0.89
CADD	Benign	6.1
DANN	Benign	0.70
PhyloP100		-0.25
PromoterAI		0.068	Neutral
Mutation Taster		=300/0	polymorphism

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: rs150737582; hg19: chr19-50979796;