4-165333801-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006745.5(MSMO1):c.255+176A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 152,016 control chromosomes in the GnomAD database, including 28,956 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.61 (28956 hom., cov: 33)
• Consequence: MSMO1 NM_006745.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.341

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 4-165333801-A-C is Benign according to our data. Variant chr4-165333801-A-C is described in ClinVar as [Benign]. Clinvar id is 1278279.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSMO1	NM_006745.5	c.255+176A>C		intron_variant		ENST00000261507.11
MSMO1	NM_001017369.3	c.-138-3988A>C		intron_variant
MSMO1	XM_005263176.3	c.255+176A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSMO1	ENST00000261507.11	c.255+176A>C		intron_variant		1	NM_006745.5	P1
MSMO1	ENST00000504317.1	c.255+176A>C		intron_variant		1
MSMO1	ENST00000393766.6	c.-138-3988A>C		intron_variant		2
MSMO1	ENST00000507013.5	c.255+176A>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92944 AN: 151898 Hom.: 28924 Cov.: 33

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.706

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.612 AC: 93033 AN: 152016 Hom.: 28956 Cov.: 33 AF XY: 0.616 AC XY: 45804 AN XY: 74302

Gnomad4 AFR AF: 0.543

Gnomad4 AMR AF: 0.670

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.674

Gnomad4 NFE AF: 0.649

Gnomad4 OTH AF: 0.607

Alfa AF: 0.623 Hom.: 3685

Bravo AF: 0.608

Asia WGS AF: 0.529 AC: 1842 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	8.3
Dann	Benign	0.58

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

Other links and lift over

dbSNP: rs1550271; hg19: chr4-166254953;