Variant 4-107895714-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001375905.1(SGMS2):c.161A>G(p.Lys54Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000147 in 1,613,996 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00078 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000081 ( 0 hom. )

Consequence

SGMS2
NM_001375905.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.39

Variant links:

Genes affected

SGMS2 (HGNC:28395): (sphingomyelin synthase 2) Sphingomyelin, a major component of cell and Golgi membranes, is made by the transfer of phosphocholine from phosphatidylcholine onto ceramide, with diacylglycerol as a side product. The protein encoded by this gene is an enzyme that catalyzes this reaction primarily at the cell membrane. The synthesis is reversible, and this enzyme can catalyze the reaction in either direction. The encoded protein is required for cell growth. Three transcript variants encoding the same protein have been found for this gene. There is evidence for more variants, but the full-length nature of their transcripts has not been determined.[provided by RefSeq, Oct 2008]

SGMS2 links:

CYP2U1-AS1 (HGNC:54817): (CYP2U1 and SGMS2 antisense RNA 1)

CYP2U1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006359458).

BP6

Variant 4-107895714-A-G is Benign according to our data. Variant chr4-107895714-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2040721.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 119 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGMS2	NM_001375905.1 linkuse as main transcript	c.161A>G	p.Lys54Arg	missense_variant	3/7	ENST00000690982.1
CYP2U1-AS1	NR_125929.1 linkuse as main transcript	n.150-2077T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGMS2	ENST00000690982.1 linkuse as main transcript	c.161A>G	p.Lys54Arg	missense_variant	3/7		NM_001375905.1	P1
CYP2U1-AS1	ENST00000656249.1 linkuse as main transcript	n.290-2077T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000782

AC:

119

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000207

AC:

AN:

250870

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

135562

show subpopulations

Gnomad AFR exome

AF:

0.00277

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000807

AC:

118

AN:

1461686

Hom.:

Cov.:

AF XY:

0.0000701

AC XY:

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.00278

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000781

AC:

119

AN:

152310

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00265

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000165

Hom.:

Bravo

AF:

0.00102

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000231

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 24, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.24

T;T;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.083

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.71

.;.;T

M_CAP

Benign

0.0056

MetaRNN

Benign

0.0064

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.095

N;N;N

MutationTaster

Benign

0.56

D;D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

0.18

N;N;N

REVEL

Benign

0.025

Sift

Benign

0.67

T;T;T

Sift4G

Benign

0.54

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.041

MVP

0.27

MPC

0.29

ClinPred

0.022

GERP RS

4.5

Varity_R

0.067

gMVP

0.22

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