4-165337836-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_006745.5(MSMO1):​c.303T>C​(p.Leu101Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

MSMO1
NM_006745.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.247
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
Variant 4-165337836-T-C is Benign according to our data. Variant chr4-165337836-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 728211.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.247 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MSMO1NM_006745.5 linkc.303T>C p.Leu101Leu synonymous_variant Exon 3 of 6 ENST00000261507.11 NP_006736.1 Q15800-1
MSMO1XM_005263176.3 linkc.303T>C p.Leu101Leu synonymous_variant Exon 3 of 6 XP_005263233.1 Q15800-1
MSMO1NM_001017369.3 linkc.-91T>C 5_prime_UTR_variant Exon 2 of 5 NP_001017369.1 Q15800-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MSMO1ENST00000261507.11 linkc.303T>C p.Leu101Leu synonymous_variant Exon 3 of 6 1 NM_006745.5 ENSP00000261507.6 Q15800-1
MSMO1ENST00000504317.1 linkc.303T>C p.Leu101Leu synonymous_variant Exon 3 of 5 1 ENSP00000423633.1 D6R952
MSMO1ENST00000507013.5 linkc.303T>C p.Leu101Leu synonymous_variant Exon 3 of 5 2 ENSP00000425241.1 D6RDP9
MSMO1ENST00000393766 linkc.-91T>C 5_prime_UTR_variant Exon 2 of 5 2 ENSP00000377361.2 Q15800-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251174
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135754
show subpopulations
Gnomad AFR exome
AF:
0.0000615
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:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461266
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726970
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Oct 25, 2017
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.60
CADD
Benign
11
DANN
Benign
0.83

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.

Other links and lift over

dbSNP: rs765463805; hg19: chr4-166258988; API