rs34971233

Positions:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P466L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CYP2S1 NM_030622.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63

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

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=0.2274169).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2S1	NM_030622.8	c.1397C>G	p.Pro466Arg	missense_variant	9/9	ENST00000310054.9	NP_085125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2S1	ENST00000310054.9	c.1397C>G	p.Pro466Arg	missense_variant	9/9	1	NM_030622.8	ENSP00000308032	P1
CYP2S1	ENST00000593890.1	c.*91C>G		3_prime_UTR_variant	3/3	3		ENSP00000469850
CYP2S1	ENST00000593545.5	c.*408C>G		3_prime_UTR_variant, NMD_transcript_variant	6/6	2		ENSP00000472555

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	1.0	N;N
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

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: rs34971233; hg19: chr19-41712275; COSMIC: COSV105189390; COSMIC: COSV105189390;