chr4-165338355-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSMO1	NM_006745.5	MANE Select	c.405-297T>C		intron	N/A	NP_006736.1	Q15800-1
	MSMO1	NM_001440534.1		c.405-297T>C		intron	N/A	NP_001427463.1
	MSMO1	NM_001017369.3		c.12-297T>C		intron	N/A	NP_001017369.1	Q15800-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSMO1	ENST00000261507.11	TSL:1 MANE Select	c.405-297T>C		intron	N/A	ENSP00000261507.6	Q15800-1
	MSMO1	ENST00000504317.1	TSL:1	c.405-297T>C		intron	N/A	ENSP00000423633.1	D6R952
	MSMO1	ENST00000906532.1		c.405-297T>C		intron	N/A	ENSP00000576591.1

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

African (AFR) AF: 0.108 AC: 4465 AN: 41226

American (AMR) AF: 0.185 AC: 2802 AN: 15122

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 581 AN: 3468

East Asian (EAS) AF: 0.0114 AC: 59 AN: 5162

South Asian (SAS) AF: 0.0968 AC: 464 AN: 4794

European-Finnish (FIN) AF: 0.356 AC: 3487 AN: 9808

Middle Eastern (MID) AF: 0.280 AC: 80 AN: 286

European-Non Finnish (NFE) AF: 0.331 AC: 22403 AN: 67592

Other (OTH) AF: 0.230 AC: 478 AN: 2082

Alfa AF: 0.151 Hom.: 308

Bravo AF: 0.219

Asia WGS AF: 0.0540 AC: 190 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.32
PhyloP100		-0.077
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: rs4353858; hg19: chr4-166259507;