NM_006745.5:c.405-297T>C

Variant names:

• chr4-165338355-T-C
• rs4353858
• NM_006745.5:c.405-297T>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.405-297T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 150,448 control chromosomes in the GnomAD database, including 5,047 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (5047 hom., cov: 30)
• Consequence: MSMO1 NM_006745.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0770

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=-0.91).
• BP6: Variant 4-165338355-T-C is Benign according to our data. Variant chr4-165338355-T-C is described in ClinVar as [Benign]. Clinvar id is 1250037.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSMO1	NM_006745.5	c.405-297T>C		intron_variant	Intron 3 of 5	ENST00000261507.11	NP_006736.1
MSMO1	NM_001017369.3	c.12-297T>C		intron_variant	Intron 2 of 4		NP_001017369.1
MSMO1	XM_005263176.3	c.405-297T>C		intron_variant	Intron 3 of 5		XP_005263233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSMO1	ENST00000261507.11	c.405-297T>C		intron_variant	Intron 3 of 5	1	NM_006745.5	ENSP00000261507.6
MSMO1	ENST00000504317.1	c.405-297T>C		intron_variant	Intron 3 of 4	1		ENSP00000423633.1
MSMO1	ENST00000507013.5	c.405-297T>C		intron_variant	Intron 3 of 4	2		ENSP00000425241.1
MSMO1	ENST00000393766.6	c.12-297T>C		intron_variant	Intron 2 of 4	2		ENSP00000377361.2

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35184 AN: 150356 Hom.: 5050 Cov.: 30

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0114

Gnomad SAS AF: 0.0973

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.234 AC: 35169 AN: 150448 Hom.: 5047 Cov.: 30 AF XY: 0.232 AC XY: 17042 AN XY: 73430

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.0114

Gnomad4 SAS AF: 0.0968

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.230

Alfa AF: 0.152 Hom.: 300

Bravo AF: 0.219

Asia WGS AF: 0.0540 AC: 190 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: 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	-0.91
CADD	Benign	2.6
DANN	Benign	0.32

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: rs4353858; hg19: chr4-166259507;