rs10863

Positions:

• chr7-130505748-A-G
• chr7-130505748-A-T

Variant summary

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

The NM_002402.4(MEST):​c.*692A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 152,184 control chromosomes in the GnomAD database, including 48,546 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 0.80 (48546 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: MEST NM_002402.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEST	NM_002402.4	c.*692A>G		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.*692A>G		3_prime_UTR_variant	12/12	1	NM_002402.4	ENSP00000223215.4

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121145 AN: 152066 Hom.: 48514 Cov.: 33

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.762

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.799

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.797 AC: 121217 AN: 152184 Hom.: 48546 Cov.: 33 AF XY: 0.789 AC XY: 58706 AN XY: 74402

Gnomad4 AFR AF: 0.740

Gnomad4 AMR AF: 0.754

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.712

Gnomad4 SAS AF: 0.762

Gnomad4 FIN AF: 0.790

Gnomad4 NFE AF: 0.849

Gnomad4 OTH AF: 0.793

Alfa AF: 0.836 Hom.: 74298

Bravo AF: 0.791

Asia WGS AF: 0.720 AC: 2504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.72

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: rs10863; hg19: chr7-130145589;