rs17046216

Positions:

• chr4-165334552-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006745.5(MSMO1):​c.255+927T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,010 control chromosomes in the GnomAD database, including 9,830 homozygotes. 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: 𝑓 0.34 (9830 hom., cov: 32)
• Consequence: MSMO1 NM_006745.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSMO1	NM_006745.5	c.255+927T>A		intron_variant		ENST00000261507.11	NP_006736.1
MSMO1	NM_001017369.3	c.-138-3237T>A		intron_variant			NP_001017369.1
MSMO1	XM_005263176.3	c.255+927T>A		intron_variant			XP_005263233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSMO1	ENST00000261507.11	c.255+927T>A		intron_variant		1	NM_006745.5	ENSP00000261507.6
MSMO1	ENST00000504317.1	c.255+927T>A		intron_variant		1		ENSP00000423633.1
MSMO1	ENST00000507013.5	c.255+927T>A		intron_variant		2		ENSP00000425241.1
MSMO1	ENST00000393766.6	c.-138-3237T>A		intron_variant		2		ENSP00000377361.2

Frequencies

GnomAD3 genomes AF: 0.342 AC: 52013 AN: 151892 Hom.: 9807 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.0115

Gnomad SAS AF: 0.0990

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.343 AC: 52079 AN: 152010 Hom.: 9830 Cov.: 32 AF XY: 0.338 AC XY: 25141 AN XY: 74314

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.0116

Gnomad4 SAS AF: 0.0989

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.311

Alfa AF: 0.318 Hom.: 4579

Bravo AF: 0.340

Asia WGS AF: 0.0790 AC: 276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.6
DANN	Benign	0.81

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: rs17046216; hg19: chr4-166255704;