chr10-95067362-TA-T

Variant names:

• chr10-95067362-TA-T
• rs11572078
• NM_000770.3:c.332-6delT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000770.3(CYP2C8):​c.332-6delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 19)
• Consequence: CYP2C8 NM_000770.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.927
• Publications: 0 publications found

Genes affected

CYP2C8 (HGNC:2622): (cytochrome P450 family 2 subfamily C member 8) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and its expression is induced by phenobarbital. The enzyme is known to metabolize many xenobiotics, including the anticonvulsive drug mephenytoin, benzo(a)pyrene, 7-ethyoxycoumarin, and the anti-cancer drug taxol. This gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000770.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C8	NM_000770.3	MANE Select	c.332-6delT		splice_region intron	N/A	NP_000761.3
	CYP2C8	NM_001198853.1		c.122-6delT		splice_region intron	N/A	NP_001185782.1
	CYP2C8	NM_001198855.1		c.122-6delT		splice_region intron	N/A	NP_001185784.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C8	ENST00000371270.6	TSL:1 MANE Select	c.332-6delT		splice_region intron	N/A	ENSP00000360317.3
	CYP2C8	ENST00000628935.1	TSL:5	c.68delT	p.Leu23TyrfsTer2	frameshift	Exon 1 of 6	ENSP00000487145.1
	CYP2C8	ENST00000479946.2	TSL:2	n.630delT		non_coding_transcript_exon	Exon 2 of 8

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs11572078; hg19: chr10-96827119; COSMIC: COSV100987964;