chr7-130505748-A-G

Variant names:

• chr7-130505748-A-G
• rs10863
• NM_002402.4:c.*692A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MEST	NM_002402.4	c.*692A>G		3_prime_UTR_variant	Exon 12 of 12	ENST00000223215.10	NP_002393.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEST	ENST00000223215.10	c.*692A>G		3_prime_UTR_variant	Exon 12 of 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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.740 AC: 30731 AN: 41528

American (AMR) AF: 0.754 AC: 11537 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.817 AC: 2836 AN: 3472

East Asian (EAS) AF: 0.712 AC: 3686 AN: 5180

South Asian (SAS) AF: 0.762 AC: 3666 AN: 4812

European-Finnish (FIN) AF: 0.790 AC: 8351 AN: 10570

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.849 AC: 57745 AN: 68018

Other (OTH) AF: 0.793 AC: 1671 AN: 2106

Alfa AF: 0.825 Hom.: 124269

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
PhyloP100		-0.073
Mutation Taster		=100/0	polymorphism (auto)

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: rs10863; hg19: chr7-130145589;