Genetic Variant MSMO1:p.Ala60Asp (chr4-165333549-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006745.5(MSMO1):c.179C>A(p.Ala60Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A60G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

MSMO1
NM_006745.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0960

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

microcephaly-congenital cataract-psoriasiform dermatitis syndrome
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

MSMO1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13956803).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006745.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MSMO1	NM_006745.5	MANE Select	c.179C>A	p.Ala60Asp	missense	Exon 2 of 6	NP_006736.1	Q15800-1
MSMO1	NM_001440534.1		c.179C>A	p.Ala60Asp	missense	Exon 2 of 6	NP_001427463.1
MSMO1	NM_001017369.3		c.-138-4240C>A		intron	N/A	NP_001017369.1	Q15800-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MSMO1	ENST00000261507.11	TSL:1 MANE Select	c.179C>A	p.Ala60Asp	missense	Exon 2 of 6	ENSP00000261507.6	Q15800-1
MSMO1	ENST00000504317.1	TSL:1	c.179C>A	p.Ala60Asp	missense	Exon 2 of 5	ENSP00000423633.1	D6R952
MSMO1	ENST00000906532.1		c.179C>A	p.Ala60Asp	missense	Exon 3 of 7	ENSP00000576591.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

247774

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.75

DEOGEN2

Uncertain

0.48

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.81

M_CAP

Benign

0.024

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.7

PhyloP100

0.096

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.25

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.0070

Polyphen

0.055

Vest4

0.55

MutPred

0.53

Loss of helix (P = 0.2022)

MVP

0.16

MPC

0.48

ClinPred

0.16

GERP RS

-4.6

Varity_R

0.31

gMVP

0.88

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over