rs78074704

Variant names:

• chr18-51196775-CGCCGCCGCG-C
• rs78074704
• NM_016626.5:c.537_545delCGCGGCGGC

Your query was ambiguous. Multiple possible variants found:

• chr18-51196775-CGCCGCCGCG-C
• chr18-51196775-CGCCGCCGCG-CGCCGCCGCGGCCGCCGCG

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BA1

The NM_016626.5(MEX3C):​c.537_545delCGCGGCGGC​(p.Ala180_Ala182del) variant causes a disruptive 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 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.45
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016626.5. 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
	MEX3C	NM_016626.5	MANE Select	c.537_545delCGCGGCGGC	p.Ala180_Ala182del	disruptive_inframe_deletion	Exon 1 of 2	NP_057710.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEX3C	ENST00000406189.4	TSL:1 MANE Select	c.537_545delCGCGGCGGC	p.Ala180_Ala182del	disruptive_inframe_deletion	Exon 1 of 2	ENSP00000385610.3	Q5U5Q3
	MEX3C	ENST00000591040.2	TSL:2	c.-107-19208_-107-19200delCGCGGCGGC		intron	N/A	ENSP00000502049.1	A0A6Q8PG18
	MEX3C	ENST00000592416.1	TSL:6	c.-25_-17delCGCGGCGGC		upstream_gene	N/A	ENSP00000468078.1	K7ER23

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

GnomAD2 exomes AF: 0.399 AC: 47370 AN: 118666 AF XY: 0.400

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 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

African (AFR) AF: 0.188 AC: 5453 AN: 29024

American (AMR) AF: 0.352 AC: 11758 AN: 33426

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 11557 AN: 24450

East Asian (EAS) AF: 0.218 AC: 7528 AN: 34490

South Asian (SAS) AF: 0.366 AC: 28455 AN: 77670

European-Finnish (FIN) AF: 0.440 AC: 15851 AN: 36056

Middle Eastern (MID) AF: 0.384 AC: 2059 AN: 5368

European-Non Finnish (NFE) AF: 0.451 AC: 482961 AN: 1071736

Other (OTH) AF: 0.400 AC: 22825 AN: 57092

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

African (AFR) AF: 0.191 AC: 7917 AN: 41428

American (AMR) AF: 0.355 AC: 5420 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1594 AN: 3468

East Asian (EAS) AF: 0.232 AC: 1179 AN: 5090

South Asian (SAS) AF: 0.354 AC: 1698 AN: 4796

European-Finnish (FIN) AF: 0.418 AC: 4402 AN: 10526

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.450 AC: 30514 AN: 67738

Other (OTH) AF: 0.367 AC: 775 AN: 2110

Alfa AF: 0.415 Hom.: 2291

Bravo AF: 0.340

ClinVar

ClinVar submissions

Significance: 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
PhyloP100		3.5
Mutation Taster		=147/53	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs78074704; hg19: chr18-48723145; COSMIC: COSV68529477; COSMIC: COSV68529477;