rs1050582

Positions:

• chr7-130505102-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002402.4(MEST):​c.*46G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 1,357,274 control chromosomes in the GnomAD database, including 196,551 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.47 (18255 hom., cov: 32)
  • Exomes 𝑓: 0.54 (178296 hom.)
• Consequence: MEST NM_002402.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170

Genes affected

MEST (HGNC:7028): (mesoderm specific transcript) This gene encodes a member of the alpha/beta hydrolase superfamily. It is imprinted, exhibiting preferential expression from the paternal allele in fetal tissues, and isoform-specific imprinting in lymphocytes. The loss of imprinting of this gene has been linked to certain types of cancer and may be due to promotor switching. The encoded protein may play a role in development. Alternatively spliced transcript variants encoding multiple isoforms have been identified for this gene. Pseudogenes of this gene are located on the short arm of chromosomes 3 and 4, and the long arm of chromosomes 6 and 15. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEST	NM_002402.4	c.*46G>C		3_prime_UTR_variant	12/12	ENST00000223215.10	NP_002393.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEST	ENST00000223215.10	c.*46G>C		3_prime_UTR_variant	12/12	1	NM_002402.4	ENSP00000223215

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71642 AN: 151930 Hom.: 18240 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.482

GnomAD3 exomes AF: 0.525 AC: 130355 AN: 248060 Hom.: 34951 AF XY: 0.525 AC XY: 70474 AN XY: 134172

Gnomad AFR exome AF: 0.257

Gnomad AMR exome AF: 0.545

Gnomad ASJ exome AF: 0.523

Gnomad EAS exome AF: 0.595

Gnomad SAS exome AF: 0.492

Gnomad FIN exome AF: 0.563

Gnomad NFE exome AF: 0.550

Gnomad OTH exome AF: 0.522

GnomAD4 exome AF: 0.540 AC: 650313 AN: 1205226 Hom.: 178296 Cov.: 16 AF XY: 0.538 AC XY: 328968 AN XY: 611834

Gnomad4 AFR exome AF: 0.261

Gnomad4 AMR exome AF: 0.545

Gnomad4 ASJ exome AF: 0.519

Gnomad4 EAS exome AF: 0.608

Gnomad4 SAS exome AF: 0.487

Gnomad4 FIN exome AF: 0.563

Gnomad4 NFE exome AF: 0.551

Gnomad4 OTH exome AF: 0.523

GnomAD4 genome AF: 0.472 AC: 71695 AN: 152048 Hom.: 18255 Cov.: 32 AF XY: 0.474 AC XY: 35210 AN XY: 74290

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.594

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.480

Alfa AF: 0.504 Hom.: 3710

Bravo AF: 0.463

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	12
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs1050582; hg19: chr7-130144943; COSMIC: COSV56230298; COSMIC: COSV56230298;