11-118534089-G-A

Variant names:

• chr11-118534089-G-A
• rs6589664
• NM_032780.4:c.897G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_032780.4(TMEM25):​c.897G>A​(p.Pro299Pro) 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
• Publications: 28 publications found

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

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

• BP4: Computational evidence support a benign effect (REVEL=0.041).
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032780.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM25	NM_032780.4	MANE Select	c.897G>A	p.Pro299Pro	synonymous	Exon 7 of 9	NP_116169.2
	TMEM25	NM_001318755.2		c.897G>A	p.Pro299Pro	synonymous	Exon 7 of 9	NP_001305684.1
	TMEM25	NM_001144037.2		c.897G>A	p.Pro299Pro	synonymous	Exon 7 of 9	NP_001137509.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM25	ENST00000313236.10	TSL:1 MANE Select	c.897G>A	p.Pro299Pro	synonymous	Exon 7 of 9	ENSP00000315635.5
	TMEM25	ENST00000533102.5	TSL:1	c.897G>A	p.Pro299Pro	synonymous	Exon 7 of 9	ENSP00000431548.1
	TMEM25	ENST00000359862.8	TSL:1	c.765G>A	p.Pro255Pro	synonymous	Exon 6 of 8	ENSP00000352924.4

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

GnomAD2 exomes AF: 0.302 AC: 75803 AN: 251396 AF XY: 0.287

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 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

African (AFR) AF: 0.181 AC: 6045 AN: 33480

American (AMR) AF: 0.537 AC: 24018 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 7734 AN: 26136

East Asian (EAS) AF: 0.312 AC: 12388 AN: 39700

South Asian (SAS) AF: 0.152 AC: 13098 AN: 86256

European-Finnish (FIN) AF: 0.312 AC: 16689 AN: 53408

Middle Eastern (MID) AF: 0.286 AC: 1651 AN: 5768

European-Non Finnish (NFE) AF: 0.290 AC: 322529 AN: 1111936

Other (OTH) AF: 0.275 AC: 16635 AN: 60394

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

African (AFR) AF: 0.189 AC: 7842 AN: 41454

American (AMR) AF: 0.411 AC: 6271 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1069 AN: 3470

East Asian (EAS) AF: 0.267 AC: 1379 AN: 5160

South Asian (SAS) AF: 0.141 AC: 678 AN: 4810

European-Finnish (FIN) AF: 0.308 AC: 3247 AN: 10550

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19810 AN: 67906

Other (OTH) AF: 0.291 AC: 614 AN: 2108

Alfa AF: 0.292 Hom.: 9398

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.68
DANN	Benign	0.85
PhyloP100		-2.7
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: rs6589664; hg19: chr11-118404804; COSMIC: COSV57096347; COSMIC: COSV57096347;