rs113939225

Variant names:

• chr10-95069236-T-A
• rs113939225
• NM_000770.3:c.167A>T

Your query was ambiguous. Multiple possible variants found:

• chr10-95069236-T-A
• chr10-95069236-T-C

Variant summary

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

The NM_001198853.1(CYP2C8):​c.-82A>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000000684 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CYP2C8 NM_001198853.1 5_prime_UTR_premature_start_codon_gain
• Scores: Splicing: ADA: 0.4206
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.33
• 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_001198853.1. 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
	CYP2C8	NM_000770.3	MANE Select	c.167A>T	p.Asn56Ile	missense splice_region	Exon 1 of 9	NP_000761.3	P10632-1
	CYP2C8	NM_001198853.1		c.-82A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	NP_001185782.1	P10632
	CYP2C8	NM_001198855.1		c.-144A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_001185784.1	P10632

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C8	ENST00000371270.6	TSL:1 MANE Select	c.167A>T	p.Asn56Ile	missense splice_region	Exon 1 of 9	ENSP00000360317.3	P10632-1
	CYP2C8	ENST00000623108.3	TSL:2	c.-82A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000485110.1	B7Z1F5
	CYP2C8	ENST00000535898.5	TSL:2	c.-15A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000445062.1	P10632-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461832 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727216

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111988

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.3
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-4.4	D
REVEL	Benign	0.18
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.67	P
Vest4		0.30
MutPred		0.53		Gain of ubiquitination at K59 (P = 0.1278)
MVP		0.77
MPC		0.098
ClinPred		0.95	D
GERP RS		2.2
PromoterAI		-0.048	Neutral
Varity_R		0.81
gMVP		0.26
Mutation Taster		=49/51	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.42
dbscSNV1_RF	Benign	0.59
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.27		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs113939225; hg19: chr10-96828993;