Variant 4-165337829-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006745.5(MSMO1):c.296A>G(p.Lys99Arg) variant causes a missense change. The variant allele was found at a frequency of 0.002 in 1,613,670 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 10 hom. )

Consequence

MSMO1
NM_006745.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.21

Variant links:

Genes affected

MSMO1 (HGNC:10545): (methylsterol monooxygenase 1) Sterol-C4-mehtyl oxidase-like protein was isolated based on its similarity to the yeast ERG25 protein. It contains a set of putative metal binding motifs with similarity to that seen in a family of membrane desaturases-hydroxylases. The protein is localized to the endoplasmic reticulum membrane and is believed to function in cholesterol biosynthesis. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MSMO1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006923169).

BP6

Variant 4-165337829-A-G is Benign according to our data. Variant chr4-165337829-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 742157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MSMO1	NM_006745.5 linkuse as main transcript	c.296A>G	p.Lys99Arg	missense_variant	3/6	ENST00000261507.11
MSMO1	XM_005263176.3 linkuse as main transcript	c.296A>G	p.Lys99Arg	missense_variant	3/6
MSMO1	NM_001017369.3 linkuse as main transcript	c.-98A>G		5_prime_UTR_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSMO1	ENST00000261507.11 linkuse as main transcript	c.296A>G	p.Lys99Arg	missense_variant	3/6	1	NM_006745.5	P1	Q15800-1
MSMO1	ENST00000504317.1 linkuse as main transcript	c.296A>G	p.Lys99Arg	missense_variant	3/5	1
MSMO1	ENST00000507013.5 linkuse as main transcript	c.296A>G	p.Lys99Arg	missense_variant	3/5	2
MSMO1	ENST00000393766.6 linkuse as main transcript	c.-98A>G		5_prime_UTR_variant	2/5	2			Q15800-2

Frequencies

GnomAD3 genomes

AF:

0.00294

AC:

447

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0199

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00319

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00308

AC:

773

AN:

251154

Hom.:

AF XY:

0.00292

AC XY:

396

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0213

Gnomad NFE exome

AF:

0.00257

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00191

AC:

2785

AN:

1461364

Hom.:

Cov.:

AF XY:

0.00190

AC XY:

1379

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0184

Gnomad4 NFE exome

AF:

0.00153

Gnomad4 OTH exome

AF:

0.00144

GnomAD4 genome

AF:

0.00293

AC:

447

AN:

152306

Hom.:

Cov.:

AF XY:

0.00365

AC XY:

272

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0199

Gnomad4 NFE

AF:

0.00319

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00213

Hom.:

Bravo

AF:

0.000820

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.00292

AC:

354

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00120

EpiControl

AF:

0.00124

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	MSMO1: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 02, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;T;T

Eigen

Benign

-0.071

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.81

T;T;T

MetaRNN

Benign

0.0069

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.060

Sift

Benign

0.34

T;T;T

Sift4G

Benign

0.37

T;T;T

Polyphen

0.0040

B;.;B

Vest4

0.38

MVP

0.51

MPC

0.25

ClinPred

0.029

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.73

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