rs17046216

Variant names:

• chr4-165334552-T-A
• rs17046216
• NM_006745.5:c.255+927T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 26 publications found

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]

MSMO1 Gene-Disease associations (from GenCC):

• microcephaly-congenital cataract-psoriasiform dermatitis syndrome

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006745.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSMO1	NM_006745.5	MANE Select	c.255+927T>A		intron	N/A	NP_006736.1
	MSMO1	NM_001440534.1		c.255+927T>A		intron	N/A	NP_001427463.1
	MSMO1	NM_001017369.3		c.-138-3237T>A		intron	N/A	NP_001017369.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSMO1	ENST00000261507.11	TSL:1 MANE Select	c.255+927T>A		intron	N/A	ENSP00000261507.6
	MSMO1	ENST00000504317.1	TSL:1	c.255+927T>A		intron	N/A	ENSP00000423633.1
	MSMO1	ENST00000507013.5	TSL:2	c.255+927T>A		intron	N/A	ENSP00000425241.1

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

African (AFR) AF: 0.467 AC: 19360 AN: 41436

American (AMR) AF: 0.231 AC: 3521 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 901 AN: 3470

East Asian (EAS) AF: 0.0116 AC: 60 AN: 5184

South Asian (SAS) AF: 0.0989 AC: 477 AN: 4824

European-Finnish (FIN) AF: 0.370 AC: 3911 AN: 10558

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22747 AN: 67948

Other (OTH) AF: 0.311 AC: 657 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.6
DANN	Benign	0.81
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17046216; hg19: chr4-166255704;