10-80081936-G-T

Position:

• chr10-80081936-G-T

Variant summary

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

The NM_001270371.2(TMEM254):​c.278G>T​(p.Cys93Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 1,612,638 control chromosomes in the GnomAD database, including 143,571 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/11 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.38 (11637 hom., cov: 32)
  • Exomes 𝑓: 0.42 (131934 hom.)
• Consequence: TMEM254 NM_001270371.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258

Genes affected

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

TMEM254 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.516193E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM254	NM_025125.4	c.183G>T	p.Leu61Leu	synonymous_variant	2/4	ENST00000372281.8	NP_079401.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM254	ENST00000372281.8	c.183G>T	p.Leu61Leu	synonymous_variant	2/4	1	NM_025125.4	ENSP00000361355.3

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57418 AN: 151858 Hom.: 11644 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.386

GnomAD3 exomes AF: 0.413 AC: 103768 AN: 251284 Hom.: 22786 AF XY: 0.420 AC XY: 57118 AN XY: 135840

Gnomad AFR exome AF: 0.257

Gnomad AMR exome AF: 0.278

Gnomad ASJ exome AF: 0.400

Gnomad EAS exome AF: 0.709

Gnomad SAS exome AF: 0.442

Gnomad FIN exome AF: 0.405

Gnomad NFE exome AF: 0.424

Gnomad OTH exome AF: 0.407

GnomAD4 exome AF: 0.420 AC: 614116 AN: 1460660 Hom.: 131934 Cov.: 37 AF XY: 0.422 AC XY: 306890 AN XY: 726716

Gnomad4 AFR exome AF: 0.248

Gnomad4 AMR exome AF: 0.281

Gnomad4 ASJ exome AF: 0.403

Gnomad4 EAS exome AF: 0.694

Gnomad4 SAS exome AF: 0.443

Gnomad4 FIN exome AF: 0.408

Gnomad4 NFE exome AF: 0.421

Gnomad4 OTH exome AF: 0.423

GnomAD4 genome AF: 0.378 AC: 57428 AN: 151978 Hom.: 11637 Cov.: 32 AF XY: 0.380 AC XY: 28199 AN XY: 74262

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.707

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.387

Alfa AF: 0.402 Hom.: 17173

Bravo AF: 0.364

TwinsUK AF: 0.429 AC: 1591

ALSPAC AF: 0.426 AC: 1640

ESP6500AA AF: 0.268 AC: 1179

ESP6500EA AF: 0.428 AC: 3678

ExAC AF: 0.415 AC: 50399

Asia WGS AF: 0.530 AC: 1841 AN: 3478

EpiCase AF: 0.421

EpiControl AF: 0.422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.72
DANN	Benign	0.73
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.0000065	T
MetaSVM	Benign	-0.96	T
Vest4		0.54
ClinPred		0.00026	T
GERP RS		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs1932574; hg19: chr10-81841692; COSMIC: COSV64845686; COSMIC: COSV64845686;