rs3775317

Variant names:

• chr4-165333022-C-G
• rs3775317
• NM_006745.5:c.-31-318C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-165333022-C-G
• chr4-165333022-C-T

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.-31-318C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,008 control chromosomes in the GnomAD database, including 6,259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (6259 hom., cov: 32)
• Consequence: MSMO1 NM_006745.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.53
• Publications: 2 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=-0.89).
• BP6: Variant 4-165333022-C-G is Benign according to our data. Variant chr4-165333022-C-G is described in ClinVar as Benign. ClinVar VariationId is 1240965.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.432 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.-31-318C>G		intron	N/A	NP_006736.1	Q15800-1
	MSMO1	NM_001440534.1		c.-31-318C>G		intron	N/A	NP_001427463.1
	MSMO1	NM_001017369.3		c.-138-4767C>G		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.-31-318C>G		intron	N/A	ENSP00000261507.6	Q15800-1
	MSMO1	ENST00000504317.1	TSL:1	c.-31-318C>G		intron	N/A	ENSP00000423633.1	D6R952
	MSMO1	ENST00000906532.1		c.-31-318C>G		intron	N/A	ENSP00000576591.1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39553 AN: 151890 Hom.: 6250 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.260 AC: 39579 AN: 152008 Hom.: 6259 Cov.: 32 AF XY: 0.266 AC XY: 19741 AN XY: 74322

African (AFR) AF: 0.104 AC: 4320 AN: 41478

American (AMR) AF: 0.441 AC: 6740 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1353 AN: 3468

East Asian (EAS) AF: 0.388 AC: 2003 AN: 5160

South Asian (SAS) AF: 0.440 AC: 2128 AN: 4832

European-Finnish (FIN) AF: 0.207 AC: 2174 AN: 10522

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19864 AN: 67956

Other (OTH) AF: 0.292 AC: 615 AN: 2106

Alfa AF: 0.270 Hom.: 762

Bravo AF: 0.269

Asia WGS AF: 0.425 AC: 1473 AN: 3466

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	-0.89
CADD	Benign	0.42
DANN	Benign	0.67
PhyloP100		-1.5
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: rs3775317; hg19: chr4-166254174;