chr10-80081936-G-C

Variant names:

• chr10-80081936-G-C
• rs1932574
• ENST00000613758.4:c.278G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000613758.4(TMEM254):​c.278G>C​(p.Cys93Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/14 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: not found (cov: 32)
• Consequence: TMEM254 ENST00000613758.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258
• Publications: 28 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29643178).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM254	NM_025125.4	c.183G>C	p.Leu61Leu	synonymous_variant	Exon 2 of 4	ENST00000372281.8	NP_079401.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM254	ENST00000372281.8	c.183G>C	p.Leu61Leu	synonymous_variant	Exon 2 of 4	1	NM_025125.4	ENSP00000361355.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.0
DANN	Benign	0.73
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.87	T
PhyloP100		-0.26
Vest4		0.56
MVP		0.15
ClinPred		0.034	T
GERP RS		1.3
PromoterAI		0.0022	Neutral
Mutation Taster		=100/0	polymorphism

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: rs1932574; hg19: chr10-81841692;