chr18-51196775-CGCCGCCGCG-C

Position:

• chr18-51196775-CGCCGCCGCG-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BA1

The NM_016626.5(MEX3C):​c.537_545del​(p.Ala182_Ala184del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 1,520,924 control chromosomes in the GnomAD database, including 137,337 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (10689 hom., cov: 0)
  • Exomes 𝑓: 0.43 (126648 hom.)
• Consequence: MEX3C NM_016626.5 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.45

Genes affected

MEX3C (HGNC:28040): (mex-3 RNA binding family member C) This gene encodes a member of a family of proteins with two K homology (KH) RNA-binding domains and a C-terminal RING-finger domain. The protein interacts with mRNA via the KH domains, and the protein shuttles between the nucleus and cytoplasm. Polymorphisms in this gene may contribute to hypertension. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_016626.5
• BP6: Variant 18-51196775-CGCCGCCGCG-C is Benign according to our data. Variant chr18-51196775-CGCCGCCGCG-C is described in ClinVar as [Benign]. Clinvar id is 769443.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEX3C	NM_016626.5	c.537_545del	p.Ala182_Ala184del	inframe_deletion	1/2	ENST00000406189.4
MEX3C	XM_047437540.1	c.537_545del	p.Ala182_Ala184del	inframe_deletion	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEX3C	ENST00000406189.4	c.537_545del	p.Ala182_Ala184del	inframe_deletion	1/2	1	NM_016626.5	P1
MEX3C	ENST00000591040.2	c.-107-19208_-107-19200del		intron_variant		2
MEX3C	ENST00000592416.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.356 AC: 53924 AN: 151500 Hom.: 10694 Cov.: 0

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.371

GnomAD3 exomes AF: 0.399 AC: 47370 AN: 118666 Hom.: 8955 AF XY: 0.400 AC XY: 26076 AN XY: 65188

Gnomad AFR exome AF: 0.246

Gnomad AMR exome AF: 0.349

Gnomad ASJ exome AF: 0.480

Gnomad EAS exome AF: 0.278

Gnomad SAS exome AF: 0.372

Gnomad FIN exome AF: 0.429

Gnomad NFE exome AF: 0.455

Gnomad OTH exome AF: 0.395

GnomAD4 exome AF: 0.430 AC: 588447 AN: 1369312 Hom.: 126648 AF XY: 0.429 AC XY: 289957 AN XY: 675622

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.352

Gnomad4 ASJ exome AF: 0.473

Gnomad4 EAS exome AF: 0.218

Gnomad4 SAS exome AF: 0.366

Gnomad4 FIN exome AF: 0.440

Gnomad4 NFE exome AF: 0.451

Gnomad4 OTH exome AF: 0.400

GnomAD4 genome AF: 0.356 AC: 53924 AN: 151612 Hom.: 10689 Cov.: 0 AF XY: 0.353 AC XY: 26166 AN XY: 74082

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.460

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.367

Alfa AF: 0.415 Hom.: 2291

Bravo AF: 0.340

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs78074704; hg19: chr18-48723145;