rs3775318

Variant names:

• chr4-165333201-C-A
• rs3775318
• NM_006745.5:c.-31-139C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-165333201-C-A
• chr4-165333201-C-G
• chr4-165333201-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006745.5(MSMO1):​c.-31-139C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000455 in 439,566 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.0000045 (0 hom.)
• Consequence: MSMO1 NM_006745.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.487
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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.-31-139C>A		intron	N/A	NP_006736.1	Q15800-1
	MSMO1	NM_001440534.1		c.-31-139C>A		intron	N/A	NP_001427463.1
	MSMO1	NM_001017369.3		c.-138-4588C>A		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.-31-139C>A		intron	N/A	ENSP00000261507.6	Q15800-1
	MSMO1	ENST00000504317.1	TSL:1	c.-31-139C>A		intron	N/A	ENSP00000423633.1	D6R952
	MSMO1	ENST00000906532.1		c.-31-139C>A		intron	N/A	ENSP00000576591.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000455 AC: 2 AN: 439566 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 227846

African (AFR) AF: 0.00 AC: 0 AN: 11834

American (AMR) AF: 0.00 AC: 0 AN: 13120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12292

East Asian (EAS) AF: 0.0000353 AC: 1 AN: 28336

South Asian (SAS) AF: 0.00 AC: 0 AN: 28530

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1798

European-Non Finnish (NFE) AF: 0.00000350 AC: 1 AN: 285510

Other (OTH) AF: 0.00 AC: 0 AN: 23964

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1314

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.56
PhyloP100		-0.49

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: rs3775318; hg19: chr4-166254353;