7-130498199-C-T

Variant names:

• chr7-130498199-C-T
• rs61735155
• NM_002402.4:c.400C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BS1 BS2

The NM_002402.4(MEST):​c.400C>T​(p.Leu134Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00324 in 1,614,156 control chromosomes in the GnomAD database, including 44 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 0.0082 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (35 hom.)
• Consequence: MEST NM_002402.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.518

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]

ENSG00000270823 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP7: Synonymous conserved (PhyloP=0.518 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00822 (1252/152284) while in subpopulation AFR AF = 0.0216 (898/41560). AF 95% confidence interval is 0.0204. There are 9 homozygotes in GnomAd4. There are 581 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
• BS2: High AC in GnomAd4 at 1252 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEST	NM_002402.4	c.400C>T	p.Leu134Leu	synonymous_variant	Exon 5 of 12	ENST00000223215.10	NP_002393.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEST	ENST00000223215.10	c.400C>T	p.Leu134Leu	synonymous_variant	Exon 5 of 12	1	NM_002402.4	ENSP00000223215.4

Frequencies

GnomAD3 genomes AF: 0.00821 AC: 1249 AN: 152166 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00916

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00240

Gnomad OTH AF: 0.00955

GnomAD2 exomes AF: 0.00395 AC: 992 AN: 251390 AF XY: 0.00354

Gnomad AFR exome AF: 0.0213

Gnomad AMR exome AF: 0.00682

Gnomad ASJ exome AF: 0.00317

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00241

Gnomad OTH exome AF: 0.0101

GnomAD4 exome AF: 0.00272 AC: 3982 AN: 1461872 Hom.: 35 Cov.: 33 AF XY: 0.00262 AC XY: 1909 AN XY: 727244

Gnomad4 AFR exome AF: 0.0243 AC: 813 AN: 33480

Gnomad4 AMR exome AF: 0.00789 AC: 353 AN: 44724

Gnomad4 ASJ exome AF: 0.00310 AC: 81 AN: 26136

Gnomad4 EAS exome AF: 0.0000756 AC: 3 AN: 39700

Gnomad4 SAS exome AF: 0.00119 AC: 103 AN: 86256

Gnomad4 FIN exome AF: 0.000168 AC: 9 AN: 53420

Gnomad4 NFE exome AF: 0.00195 AC: 2166 AN: 1111992

Gnomad4 Remaining exome AF: 0.00535 AC: 323 AN: 60396

GnomAD4 genome AF: 0.00822 AC: 1252 AN: 152284 Hom.: 9 Cov.: 32 AF XY: 0.00780 AC XY: 581 AN XY: 74462

Gnomad4 AFR AF: 0.0216 AC: 0.0216073 AN: 0.0216073

Gnomad4 AMR AF: 0.00915 AC: 0.00914794 AN: 0.00914794

Gnomad4 ASJ AF: 0.00490 AC: 0.00489914 AN: 0.00489914

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000415 AC: 0.000414766 AN: 0.000414766

Gnomad4 FIN AF: 0.000189 AC: 0.000188644 AN: 0.000188644

Gnomad4 NFE AF: 0.00240 AC: 0.00239642 AN: 0.00239642

Gnomad4 OTH AF: 0.00945 AC: 0.0094518 AN: 0.0094518

Alfa AF: 0.00541 Hom.: 7

Bravo AF: 0.00979

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00316

EpiControl AF: 0.00427

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	16
DANN	Benign	0.85
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61735155; hg19: chr7-130138040;