19-41090049-G-C

Variant names:

• chr19-41090049-G-C
• rs751293256
• NM_000766.5:c.346G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000766.5(CYP2A13):​c.346G>C​(p.Val116Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 151,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 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: 𝑓 0.000020 (0 hom., cov: 31)
• Consequence: CYP2A13 NM_000766.5 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234

Genes affected

CYP2A13 (HGNC:2608): (cytochrome P450 family 2 subfamily A member 13) 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. Although its endogenous substrate has not been determined, it is known to metabolize 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, a major nitrosamine specific to tobacco. This gene is part of a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18114936).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2A13	NM_000766.5	c.346G>C	p.Val116Leu	missense_variant, splice_region_variant	Exon 3 of 9	ENST00000330436.4	NP_000757.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2A13	ENST00000330436.4	c.346G>C	p.Val116Leu	missense_variant, splice_region_variant	Exon 3 of 9	1	NM_000766.5	ENSP00000332679.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 151954 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 35

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 151954 Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 2 AN XY: 74206

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	11
DANN	Benign	0.64
DEOGEN2	Benign	0.040	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.099
Sift	Benign	0.19	T
Sift4G	Benign	0.34	T
Polyphen		0.036	B
Vest4		0.14
MutPred		0.76		Loss of methylation at K112 (P = 0.0965);
MVP		0.22
MPC		0.11
ClinPred		0.19	T
GERP RS		1.1
Varity_R		0.48
gMVP		0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs751293256; hg19: chr19-41595954;