rs6589664

Positions:

• chr11-118534089-G-A
• chr11-118534089-G-C
• chr11-118534089-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_032780.4(TMEM25):​c.897G>A​(p.Pro299=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,613,730 control chromosomes in the GnomAD database, including 69,962 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 0.27 (6150 hom., cov: 31)
  • Exomes 𝑓: 0.29 (63812 hom.)
• Consequence: TMEM25 NM_032780.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70

Genes affected

TMEM25 (HGNC:25890): (transmembrane protein 25) Predicted to be involved in negative regulation of excitatory postsynaptic potential and regulation of protein stability. Predicted to be located in late endosome and lysosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=-2.7 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM25	NM_032780.4	c.897G>A	p.Pro299=	synonymous_variant	7/9	ENST00000313236.10	NP_116169.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM25	ENST00000313236.10	c.897G>A	p.Pro299=	synonymous_variant	7/9	1	NM_032780.4	ENSP00000315635	P1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41282 AN: 151814 Hom.: 6131 Cov.: 31

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.291

GnomAD3 exomes AF: 0.302 AC: 75803 AN: 251396 Hom.: 13268 AF XY: 0.287 AC XY: 39058 AN XY: 135870

Gnomad AFR exome AF: 0.183

Gnomad AMR exome AF: 0.549

Gnomad ASJ exome AF: 0.297

Gnomad EAS exome AF: 0.256

Gnomad SAS exome AF: 0.147

Gnomad FIN exome AF: 0.303

Gnomad NFE exome AF: 0.292

Gnomad OTH exome AF: 0.306

GnomAD4 exome AF: 0.288 AC: 420787 AN: 1461796 Hom.: 63812 Cov.: 46 AF XY: 0.283 AC XY: 205823 AN XY: 727198

Gnomad4 AFR exome AF: 0.181

Gnomad4 AMR exome AF: 0.537

Gnomad4 ASJ exome AF: 0.296

Gnomad4 EAS exome AF: 0.312

Gnomad4 SAS exome AF: 0.152

Gnomad4 FIN exome AF: 0.312

Gnomad4 NFE exome AF: 0.290

Gnomad4 OTH exome AF: 0.275

GnomAD4 genome AF: 0.272 AC: 41334 AN: 151934 Hom.: 6150 Cov.: 31 AF XY: 0.272 AC XY: 20229 AN XY: 74250

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.291

Alfa AF: 0.292 Hom.: 7259

Bravo AF: 0.282

Asia WGS AF: 0.194 AC: 675 AN: 3478

EpiCase AF: 0.289

EpiControl AF: 0.282

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.68
DANN	Benign	0.85

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: rs6589664; hg19: chr11-118404804; COSMIC: COSV57096347; COSMIC: COSV57096347;