10-80088158-G-C

Variant names:

• chr10-80088158-G-C
• rs728616
• NM_025125.4:c.252-2639G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001270367.1(TMEM254):​c.324-2639G>C variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM254 NM_001270367.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.579
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270367.1. 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
	TMEM254	NM_025125.4	MANE Select	c.252-2639G>C		intron	N/A	NP_079401.2
	TMEM254	NM_001270367.1		c.324-2639G>C		intron	N/A	NP_001257296.1
	TMEM254	NM_001270368.1		c.*10-2639G>C		intron	N/A	NP_001257297.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM254	ENST00000372281.8	TSL:1 MANE Select	c.252-2639G>C		intron	N/A	ENSP00000361355.3
	TMEM254	ENST00000372273.7	TSL:1	c.312-2639G>C		intron	N/A	ENSP00000361347.3
	TMEM254	ENST00000613758.4	TSL:1	c.*41-2639G>C		intron	N/A	ENSP00000482766.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.58
DANN	Benign	0.44
PhyloP100		-0.58

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: rs728616; hg19: chr10-81847914;