4-165338355-T-A

Variant names:

• chr4-165338355-T-A
• rs4353858
• NM_006745.5:c.405-297T>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006745.5(MSMO1):​c.405-297T>A variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: MSMO1 NM_006745.5 intron
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSMO1	NM_006745.5	c.405-297T>A		intron_variant	Intron 3 of 5	ENST00000261507.11	NP_006736.1
MSMO1	NM_001017369.3	c.12-297T>A		intron_variant	Intron 2 of 4		NP_001017369.1
MSMO1	XM_005263176.3	c.405-297T>A		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>A		intron_variant	Intron 3 of 5	1	NM_006745.5	ENSP00000261507.6
MSMO1	ENST00000504317.1	c.405-297T>A		intron_variant	Intron 3 of 4	1		ENSP00000423633.1
MSMO1	ENST00000507013.5	c.405-297T>A		intron_variant	Intron 3 of 4	2		ENSP00000425241.1
MSMO1	ENST00000393766.6	c.12-297T>A		intron_variant	Intron 2 of 4	2		ENSP00000377361.2

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.30

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;