rs1397665252

Variant names:

• chr19-41193352-G-T
• rs1397665252
• NM_030622.8:c.88G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-41193352-G-T
• chr19-41193352-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030622.8(CYP2S1):​c.88G>T​(p.Gly30Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000578 in 1,384,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000058 (0 hom.)
• Consequence: CYP2S1 NM_030622.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.99
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29507536).

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.88G>T	p.Gly30Cys	missense	Exon 1 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.88G>T	p.Gly30Cys	missense	Exon 1 of 9	ENSP00000308032.3	Q96SQ9-1
	CYP2S1	ENST00000922089.1		c.88G>T	p.Gly30Cys	missense	Exon 1 of 9	ENSP00000592148.1
	CYP2S1	ENST00000922088.1		c.88G>T	p.Gly30Cys	missense	Exon 1 of 8	ENSP00000592147.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000754 AC: 1 AN: 132612 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000215

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000578 AC: 8 AN: 1384314 Hom.: 0 Cov.: 31 AF XY: 0.00000587 AC XY: 4 AN XY: 681964

African (AFR) AF: 0.00 AC: 0 AN: 30198

American (AMR) AF: 0.00 AC: 0 AN: 34404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24616

East Asian (EAS) AF: 0.00 AC: 0 AN: 34760

South Asian (SAS) AF: 0.00 AC: 0 AN: 78470

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47480

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4270

European-Non Finnish (NFE) AF: 0.00000746 AC: 8 AN: 1072922

Other (OTH) AF: 0.00 AC: 0 AN: 57194

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000569 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.078	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.0
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.30
MutPred		0.41		Loss of disorder (P = 0.0225)
MVP		0.72
MPC		0.95
ClinPred		0.93	D
GERP RS		3.4
PromoterAI		-0.031	Neutral
Varity_R		0.63
gMVP		0.71
Mutation Taster		=86/14	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: rs1397665252; hg19: chr19-41699257;