Variant 19-41193319-C-A 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.55C>A(p.Leu19Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000817 in 1,541,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

CYP2S1
NM_030622.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.252

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=0.021515131).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2S1	NM_030622.8 linkuse as main transcript	c.55C>A	p.Leu19Met	missense_variant	1/9	ENST00000310054.9	NP_085125.1
CYP2S1	XM_047438711.1 linkuse as main transcript	c.55C>A	p.Leu19Met	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.55C>A	p.Leu19Met	missense_variant	1/9	1	NM_030622.8	ENSP00000308032	P1	Q96SQ9-1
CYP2S1	ENST00000600561.1 linkuse as main transcript	c.55C>A	p.Leu19Met	missense_variant	1/4	2		ENSP00000471016
CYP2S1	ENST00000597754.1 linkuse as main transcript	c.55C>A	p.Leu19Met	missense_variant	1/4	5		ENSP00000471637
CYP2S1	ENST00000593545.5 linkuse as main transcript	c.55C>A	p.Leu19Met	missense_variant, NMD_transcript_variant	1/6	2		ENSP00000472555

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.0000811

AC:

AN:

135620

Hom.:

AF XY:

0.0000816

AC XY:

AN XY:

73502

show subpopulations

Gnomad AFR exome

AF:

0.000682

Gnomad AMR exome

AF:

0.000167

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000446

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000420

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000698

AC:

AN:

1389454

Hom.:

Cov.:

AF XY:

0.0000613

AC XY:

AN XY:

685146

show subpopulations

Gnomad4 AFR exome

AF:

0.00127

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000446

Gnomad4 OTH exome

AF:

0.0000870

GnomAD4 genome

AF:

0.000190

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.000262

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

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000246

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000127

AC:

ExAC

AF:

0.0000526

AC:

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 17, 2021

The c.55C>A (p.L19M) alteration is located in exon 1 (coding exon 1) of the CYP2S1 gene. This alteration results from a C to A substitution at nucleotide position 55, causing the leucine (L) at amino acid position 19 to be replaced by a methionine (M). 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

0.16

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

T;T;T

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.38

T;T;T

M_CAP

Benign

0.069

MetaRNN

Benign

0.022

T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.0

N;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.71

N;.;.

REVEL

Benign

0.20

Sift

Benign

0.13

T;.;.

Sift4G

Uncertain

0.026

D;D;T

Polyphen

0.98

D;.;.

Vest4

0.29

MVP

0.26

MPC

0.38

ClinPred

0.027

GERP RS

1.4

Varity_R

0.17

gMVP

0.37

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