rs2301335

Variant names:

• chr7-130492985-G-A
• rs2301335
• NM_002402.4:c.26+646G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002402.4(MEST):​c.26+646G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 151,836 control chromosomes in the GnomAD database, including 17,889 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 0.46 (17889 hom., cov: 30)
• Consequence: MEST NM_002402.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002402.4. 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
	MEST	NM_002402.4	MANE Select	c.26+646G>A		intron	N/A	NP_002393.2
	MEST	NM_177524.2		c.-1-2383G>A		intron	N/A	NP_803490.1	A4D1L9
	MEST	NM_177525.2		c.-2+1499G>A		intron	N/A	NP_803491.1	Q5EB52-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEST	ENST00000223215.10	TSL:1 MANE Select	c.26+646G>A		intron	N/A	ENSP00000223215.4	Q5EB52-1
	MEST	ENST00000341441.9	TSL:1	c.-1-2383G>A		intron	N/A	ENSP00000342749.4	Q5EB52-2
	MEST	ENST00000416162.7	TSL:1	c.-1-2383G>A		intron	N/A	ENSP00000408933.2	Q5EB52-3

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70372 AN: 151718 Hom.: 17881 Cov.: 30

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.478

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.464 AC: 70416 AN: 151836 Hom.: 17889 Cov.: 30 AF XY: 0.466 AC XY: 34577 AN XY: 74156

African (AFR) AF: 0.242 AC: 10005 AN: 41402

American (AMR) AF: 0.533 AC: 8132 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1869 AN: 3468

East Asian (EAS) AF: 0.590 AC: 3037 AN: 5144

South Asian (SAS) AF: 0.495 AC: 2377 AN: 4802

European-Finnish (FIN) AF: 0.565 AC: 5943 AN: 10512

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37498 AN: 67940

Other (OTH) AF: 0.475 AC: 998 AN: 2100

Alfa AF: 0.495 Hom.: 2488

Bravo AF: 0.454

Asia WGS AF: 0.546 AC: 1898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.82
PhyloP100		-2.2
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2301335;

hg19: chr7-130132826;