19-41193277-G-C

Variant names:

• chr19-41193277-G-C
• rs202041018
• NM_030622.8:c.13G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030622.8(CYP2S1):​c.13G>C​(p.Gly5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000072 in 1,388,332 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.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CYP2S1 NM_030622.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213

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]

LOC124904790 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26691186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2S1	NM_030622.8	c.13G>C	p.Gly5Arg	missense_variant	Exon 1 of 9	ENST00000310054.9	NP_085125.1
CYP2S1	XM_047438711.1	c.13G>C	p.Gly5Arg	missense_variant	Exon 1 of 7		XP_047294667.1
LOC124904790	XM_047439802.1	c.-225C>G		upstream_gene_variant			XP_047295758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2S1	ENST00000310054.9	c.13G>C	p.Gly5Arg	missense_variant	Exon 1 of 9	1	NM_030622.8	ENSP00000308032.3
CYP2S1	ENST00000600561.1	c.13G>C	p.Gly5Arg	missense_variant	Exon 1 of 4	2		ENSP00000471016.1
CYP2S1	ENST00000597754.1	c.13G>C	p.Gly5Arg	missense_variant	Exon 1 of 4	5		ENSP00000471637.1
CYP2S1	ENST00000593545.5	n.13G>C		non_coding_transcript_exon_variant	Exon 1 of 6	2		ENSP00000472555.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.20e-7 AC: 1 AN: 1388332 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 685312

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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	0.19
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.064	T;T;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.75	T;T;T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.0	N;.;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.9	D;.;.
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D;.;.
Sift4G	Uncertain	0.0030	D;T;D
Polyphen		0.96	D;.;.
Vest4		0.25
MutPred		0.51		Gain of helix (P = 0.0128);Gain of helix (P = 0.0128);Gain of helix (P = 0.0128);
MVP		0.48
MPC		0.72
ClinPred		0.80	D
GERP RS		-0.32
Varity_R		0.40
gMVP		0.49

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: rs202041018; hg19: chr19-41699182;