Variant chr19-41193287-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_030622.8(CYP2S1):c.23C>T(p.Ala8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000188 in 1,541,084 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 1 hom. )

Consequence

CYP2S1
NM_030622.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.16

Variant links:

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]

CYP2S1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05771777).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2S1	NM_030622.8 linkuse as main transcript	c.23C>T	p.Ala8Val	missense_variant	1/9	ENST00000310054.9	NP_085125.1
CYP2S1	XM_047438711.1 linkuse as main transcript	c.23C>T	p.Ala8Val	missense_variant	1/7		XP_047294667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2S1	ENST00000310054.9 linkuse as main transcript	c.23C>T	p.Ala8Val	missense_variant	1/9	1	NM_030622.8	ENSP00000308032	P1	Q96SQ9-1
CYP2S1	ENST00000600561.1 linkuse as main transcript	c.23C>T	p.Ala8Val	missense_variant	1/4	2		ENSP00000471016
CYP2S1	ENST00000597754.1 linkuse as main transcript	c.23C>T	p.Ala8Val	missense_variant	1/4	5		ENSP00000471637
CYP2S1	ENST00000593545.5 linkuse as main transcript	c.23C>T	p.Ala8Val	missense_variant, NMD_transcript_variant	1/6	2		ENSP00000472555

Frequencies

GnomAD3 genomes

AF:

0.0000987

AC:

AN:

151926

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000145

AC:

AN:

137576

Hom.:

AF XY:

0.0000134

AC XY:

AN XY:

74750

show subpopulations

Gnomad AFR exome

AF:

0.000325

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000101

AC:

AN:

1389158

Hom.:

Cov.:

AF XY:

0.00000584

AC XY:

AN XY:

685500

show subpopulations

Gnomad4 AFR exome

AF:

0.000324

Gnomad4 AMR exome

AF:

0.0000282

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:

9.28e-7

Gnomad4 OTH exome

AF:

0.0000174

GnomAD4 genome

AF:

0.0000987

AC:

AN:

151926

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74216

show subpopulations

Gnomad4 AFR

AF:

0.000362

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000125

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2022

The c.23C>T (p.A8V) alteration is located in exon 1 (coding exon 1) of the CYP2S1 gene. This alteration results from a C to T substitution at nucleotide position 23, causing the alanine (A) at amino acid position 8 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0036

T;T;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.67

T;T;T

M_CAP

Benign

0.064

MetaRNN

Benign

0.058

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

N;.;.

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.040

N;.;.

REVEL

Benign

0.099

Sift

Benign

0.62

T;.;.

Sift4G

Benign

0.99

T;T;T

Polyphen

0.34

B;.;.

Vest4

0.097

MutPred

0.42

Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);

MVP

0.29

MPC

0.29

ClinPred

0.16

GERP RS

3.4

Varity_R

0.085

gMVP

0.51

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over