chr19-41197871-G-C

Variant names:

• chr19-41197871-G-C
• NM_030622.8:c.436G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_030622.8(CYP2S1):​c.436G>C​(p.Glu146Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CYP2S1 NM_030622.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.734

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.934

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2S1	NM_030622.8	c.436G>C	p.Glu146Gln	missense_variant	Exon 3 of 9	ENST00000310054.9	NP_085125.1
CYP2S1	XM_047438711.1	c.436G>C	p.Glu146Gln	missense_variant	Exon 3 of 7		XP_047294667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2S1	ENST00000310054.9	c.436G>C	p.Glu146Gln	missense_variant	Exon 3 of 9	1	NM_030622.8	ENSP00000308032.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461808 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727192

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.068	T;T
Eigen	Uncertain	0.30
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Uncertain	0.087	D
MetaRNN	Pathogenic	0.93	D;D
MetaSVM	Uncertain	-0.0064	T
MutationAssessor	Uncertain	2.8	M;.
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.8	D;.
REVEL	Uncertain	0.57
Sift	Uncertain	0.0070	D;.
Sift4G	Uncertain	0.043	D;T
Polyphen		0.98	D;.
Vest4		0.26
MutPred		0.89		Loss of ubiquitination at K142 (P = 0.0702);Loss of ubiquitination at K142 (P = 0.0702);
MVP		0.55
MPC		0.67
ClinPred		0.98	D
GERP RS		3.8
Varity_R		0.43
gMVP		0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-41703776;