dbSNP rs2118496: MSMO1:c.255+196A>G (chr4-165333821-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_006745.5(MSMO1):c.255+196A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 152,056 control chromosomes in the GnomAD database, including 24,791 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.57 ( 24791 hom., cov: 33)

Consequence

MSMO1
NM_006745.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.109

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 4-165333821-A-G is Benign according to our data. Variant chr4-165333821-A-G is described in ClinVar as Benign. ClinVar VariationId is 1267620.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
MSMO1	NM_006745.5	MANE Select	c.255+196A>G	intron	N/A	NP_006736.1	Q15800-1
MSMO1	NM_001440534.1		c.255+196A>G	intron	N/A	NP_001427463.1
MSMO1	NM_001017369.3		c.-138-3968A>G	intron	N/A	NP_001017369.1	Q15800-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MSMO1	ENST00000261507.11	TSL:1 MANE Select	c.255+196A>G	intron	N/A	ENSP00000261507.6	Q15800-1
MSMO1	ENST00000504317.1	TSL:1	c.255+196A>G	intron	N/A	ENSP00000423633.1	D6R952
MSMO1	ENST00000906532.1		c.255+196A>G	intron	N/A	ENSP00000576591.1

Frequencies

GnomAD3 genomes

AF:

0.568

AC:

86273

AN:

151936

Hom.:

24761

Cov.:

show subpopulations

Gnomad AFR

AF:

0.531

Gnomad AMI

AF:

0.700

Gnomad AMR

AF:

0.645

Gnomad ASJ

AF:

0.582

Gnomad EAS

AF:

0.378

Gnomad SAS

AF:

0.520

Gnomad FIN

AF:

0.577

Gnomad MID

AF:

0.582

Gnomad NFE

AF:

0.586

Gnomad OTH

AF:

0.574

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.568

AC:

86364

AN:

152056

Hom.:

24791

Cov.:

AF XY:

0.571

AC XY:

42425

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.532

AC:

22056

AN:

41462

American (AMR)

AF:

0.645

AC:

9843

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.582

AC:

2021

AN:

3472

East Asian (EAS)

AF:

0.378

AC:

1959

AN:

5186

South Asian (SAS)

AF:

0.521

AC:

2517

AN:

4828

European-Finnish (FIN)

AF:

0.577

AC:

6089

AN:

10556

Middle Eastern (MID)

AF:

0.585

AC:

172

AN:

294

European-Non Finnish (NFE)

AF:

0.586

AC:

39860

AN:

67972

Other (OTH)

AF:

0.574

AC:

1209

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1937

3874

5811

7748

9685

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

744

1488

2232

2976

3720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.580

Hom.:

11011

Bravo

AF:

0.572

Asia WGS

AF:

0.488

AC:

1696

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.0

(source)

DANN

Benign

0.47

PhyloP100

0.11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over