rs34971233

Variant names:

• chr19-41206370-C-G
• rs34971233
• NM_030622.8:c.1397C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-41206370-C-G
• chr19-41206370-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030622.8(CYP2S1):​c.1397C>G​(p.Pro466Arg) 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. 15/22 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: 31)
• Consequence: CYP2S1 NM_030622.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 15 publications found

Genes affected

CYP2S1 (HGNC:15654): (cytochrome P450 family 2 subfamily S member 1) 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. In rodents, the homologous protein has been shown to metabolize certain carcinogens; however, the specific function of the human protein has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2274169).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030622.8. 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
	CYP2S1	NM_030622.8	MANE Select	c.1397C>G	p.Pro466Arg	missense	Exon 9 of 9	NP_085125.1	Q96SQ9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2S1	ENST00000310054.9	TSL:1 MANE Select	c.1397C>G	p.Pro466Arg	missense	Exon 9 of 9	ENSP00000308032.3	Q96SQ9-1
	CYP2S1	ENST00000922089.1		c.1394C>G	p.Pro465Arg	missense	Exon 9 of 9	ENSP00000592148.1
	CYP2S1	ENST00000922088.1		c.1217C>G	p.Pro406Arg	missense	Exon 8 of 8	ENSP00000592147.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 22

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.033
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		1.6
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.22
Sift	Benign	0.57	T
Sift4G	Benign	0.60	T
Polyphen		1.0	D
Vest4		0.25
MutPred		0.40		Loss of glycosylation at P466 (P = 0.0359)
MVP		0.62
MPC		1.0
ClinPred		0.90	D
GERP RS		3.3
Varity_R		0.30
gMVP		0.45
Mutation Taster		=96/4	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: rs34971233; hg19: chr19-41712275; COSMIC: COSV105189390; COSMIC: COSV105189390;