rs728616

chr10-80088158-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025125.4(TMEM254):c.252-2639G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 151,826 control chromosomes in the GnomAD database, including 1,060 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 0.11 (1060 hom., cov: 32)
• Consequence: TMEM254 NM_025125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.579

Genes affected

TMEM254 (HGNC:25804): (transmembrane protein 254) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM254	NM_025125.4	c.252-2639G>T		intron_variant		ENST00000372281.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM254	ENST00000372281.8	c.252-2639G>T		intron_variant		1	NM_025125.4	P1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16306 AN: 151708 Hom.: 1050 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.0793

Gnomad EAS AF: 0.0172

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.0545

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0819

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.108 AC: 16352 AN: 151826 Hom.: 1060 Cov.: 32 AF XY: 0.110 AC XY: 8170 AN XY: 74192

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.0793

Gnomad4 EAS AF: 0.0172

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.0545

Gnomad4 NFE AF: 0.0818

Gnomad4 OTH AF: 0.129

Alfa AF: 0.0893 Hom.: 1431

Bravo AF: 0.118

Asia WGS AF: 0.138 AC: 479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.55
Dann	Benign	0.51

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: rs728616; hg19: chr10-81847914;