4-165337885-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006745.5(MSMO1):c.352T>C(p.Tyr118His) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,460,982 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

MSMO1
NM_006745.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.24

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19946161).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MSMO1	NM_006745.5 linkuse as main transcript	c.352T>C	p.Tyr118His	missense_variant	3/6	ENST00000261507.11
MSMO1	XM_005263176.3 linkuse as main transcript	c.352T>C	p.Tyr118His	missense_variant	3/6
MSMO1	NM_001017369.3 linkuse as main transcript	c.-42T>C		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.352T>C	p.Tyr118His	missense_variant	3/6	1	NM_006745.5	P1	Q15800-1
MSMO1	ENST00000504317.1 linkuse as main transcript	c.352T>C	p.Tyr118His	missense_variant	3/5	1
MSMO1	ENST00000507013.5 linkuse as main transcript	c.352T>C	p.Tyr118His	missense_variant	3/5	2
MSMO1	ENST00000393766.6 linkuse as main transcript	c.-42T>C		5_prime_UTR_variant	2/5	2			Q15800-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251028

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135680

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000441

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1460982

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726868

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000126

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Feb 04, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with MSMO1-related conditions. This variant is present in population databases (rs755943539, gnomAD 0.004%). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 118 of the MSMO1 protein (p.Tyr118His). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.38

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.22

T;T;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.072

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

T;T;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.24

N;N;N

REVEL

Benign

0.070

Sift

Benign

0.54

T;T;T

Sift4G

Benign

0.54

T;T;T

Polyphen

0.0030

B;.;B

Vest4

0.56

MutPred

0.68

Gain of relative solvent accessibility (P = 0.1259);Gain of relative solvent accessibility (P = 0.1259);Gain of relative solvent accessibility (P = 0.1259);

MVP

0.23

MPC

0.39

ClinPred

0.31

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.054

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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