rs3741324

Variant names:

• chr11-118535120-G-A
• rs3741324
• NM_032780.4:c.*540G>A

Variant summary

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

The NM_032780.4(TMEM25):​c.*540G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,016,926 control chromosomes in the GnomAD database, including 11,554 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 0.16 (2453 hom., cov: 32)
  • Exomes 𝑓: 0.14 (9101 hom.)
• Consequence: TMEM25 NM_032780.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.494
• Publications: 17 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM25	NM_032780.4	MANE Select	c.*540G>A		3_prime_UTR	Exon 9 of 9	NP_116169.2
	TMEM25	NM_001144034.2		c.*540G>A		3_prime_UTR	Exon 8 of 8	NP_001137506.1	Q86YD3-2
	TMEM25	NM_001144035.2		c.*540G>A		3_prime_UTR	Exon 8 of 8	NP_001137507.1	Q86YD3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM25	ENST00000313236.10	TSL:1 MANE Select	c.*540G>A		3_prime_UTR	Exon 9 of 9	ENSP00000315635.5	Q86YD3-1
	TMEM25	ENST00000359862.8	TSL:1	c.*540G>A		3_prime_UTR	Exon 8 of 8	ENSP00000352924.4	Q86YD3-2
	TMEM25	ENST00000533102.5	TSL:1	c.1025-388G>A		intron	N/A	ENSP00000431548.1	E9PKP3

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24505 AN: 151918 Hom.: 2456 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0962

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.138 AC: 119110 AN: 864890 Hom.: 9101 Cov.: 33 AF XY: 0.138 AC XY: 55471 AN XY: 400698

African (AFR) AF: 0.173 AC: 2911 AN: 16782

American (AMR) AF: 0.0757 AC: 237 AN: 3130

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 856 AN: 6126

East Asian (EAS) AF: 0.484 AC: 2498 AN: 5166

South Asian (SAS) AF: 0.328 AC: 5917 AN: 18014

European-Finnish (FIN) AF: 0.148 AC: 306 AN: 2062

Middle Eastern (MID) AF: 0.160 AC: 276 AN: 1720

European-Non Finnish (NFE) AF: 0.129 AC: 101123 AN: 782714

Other (OTH) AF: 0.171 AC: 4986 AN: 29176

GnomAD4 genome AF: 0.161 AC: 24518 AN: 152036 Hom.: 2453 Cov.: 32 AF XY: 0.166 AC XY: 12308 AN XY: 74334

African (AFR) AF: 0.174 AC: 7224 AN: 41450

American (AMR) AF: 0.0960 AC: 1467 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 513 AN: 3468

East Asian (EAS) AF: 0.493 AC: 2532 AN: 5140

South Asian (SAS) AF: 0.338 AC: 1629 AN: 4824

European-Finnish (FIN) AF: 0.163 AC: 1727 AN: 10574

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8923 AN: 67988

Other (OTH) AF: 0.157 AC: 332 AN: 2110

Alfa AF: 0.133 Hom.: 1570

Bravo AF: 0.155

Asia WGS AF: 0.424 AC: 1472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	11
DANN	Benign	0.78
PhyloP100		0.49
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: rs3741324; hg19: chr11-118405835; COSMIC: COSV57096954; COSMIC: COSV57096954;