19-41193352-G-A

Variant names:

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

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.88G>A​(p.Gly30Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,384,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. G30C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CYP2S1 NM_030622.8 missense
• Clinical Significance: Not reported in ClinVar
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21125486).

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>A	p.Gly30Ser	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>A	p.Gly30Ser	missense	Exon 1 of 9	ENSP00000308032.3	Q96SQ9-1
	CYP2S1	ENST00000922089.1		c.88G>A	p.Gly30Ser	missense	Exon 1 of 9	ENSP00000592148.1
	CYP2S1	ENST00000922088.1		c.88G>A	p.Gly30Ser	missense	Exon 1 of 8	ENSP00000592147.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1384314 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 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: 9.32e-7 AC: 1 AN: 1072922

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.062	T
Eigen	Benign	0.070
Eigen_PC	Benign	0.050
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.0
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.21
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.054	T
Polyphen		1.0	D
Vest4		0.12
MutPred		0.22		Gain of phosphorylation at G30 (P = 0.025)
MVP		0.67
MPC		0.79
ClinPred		0.84	D
GERP RS		3.4
PromoterAI		-0.050	Neutral
Varity_R		0.22
gMVP		0.56
Mutation Taster		=88/12	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;