chr4-165333201-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006745.5(MSMO1):​c.-31-139C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 590,456 control chromosomes in the GnomAD database, including 106,119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (23650 hom., cov: 33)
  • Exomes 𝑓: 0.60 (82469 hom.)
• Consequence: MSMO1 NM_006745.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 4-165333201-C-G is Benign according to our data. Variant chr4-165333201-C-G is described in ClinVar as Benign. ClinVar VariationId is 1270307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.641 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.-31-139C>G		intron	N/A	NP_006736.1	Q15800-1
	MSMO1	NM_001440534.1		c.-31-139C>G		intron	N/A	NP_001427463.1
	MSMO1	NM_001017369.3		c.-138-4588C>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.-31-139C>G		intron	N/A	ENSP00000261507.6	Q15800-1
	MSMO1	ENST00000504317.1	TSL:1	c.-31-139C>G		intron	N/A	ENSP00000423633.1	D6R952
	MSMO1	ENST00000906532.1		c.-31-139C>G		intron	N/A	ENSP00000576591.1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 81043 AN: 151946 Hom.: 23637 Cov.: 33

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.552

GnomAD4 exome AF: 0.605 AC: 265065 AN: 438390 Hom.: 82469 AF XY: 0.606 AC XY: 137660 AN XY: 227272

African (AFR) AF: 0.284 AC: 3355 AN: 11814

American (AMR) AF: 0.658 AC: 8616 AN: 13096

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 6508 AN: 12272

East Asian (EAS) AF: 0.353 AC: 9973 AN: 28284

South Asian (SAS) AF: 0.600 AC: 17070 AN: 28448

European-Finnish (FIN) AF: 0.642 AC: 21878 AN: 34088

Middle Eastern (MID) AF: 0.611 AC: 1096 AN: 1794

European-Non Finnish (NFE) AF: 0.641 AC: 182621 AN: 284694

Other (OTH) AF: 0.584 AC: 13948 AN: 23900

GnomAD4 genome AF: 0.533 AC: 81077 AN: 152066 Hom.: 23650 Cov.: 33 AF XY: 0.538 AC XY: 40015 AN XY: 74328

African (AFR) AF: 0.288 AC: 11938 AN: 41464

American (AMR) AF: 0.640 AC: 9780 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1833 AN: 3468

East Asian (EAS) AF: 0.380 AC: 1967 AN: 5178

South Asian (SAS) AF: 0.591 AC: 2848 AN: 4818

European-Finnish (FIN) AF: 0.648 AC: 6845 AN: 10566

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43888 AN: 67968

Other (OTH) AF: 0.554 AC: 1171 AN: 2112

Alfa AF: 0.439 Hom.: 1314

Bravo AF: 0.521

Asia WGS AF: 0.524 AC: 1812 AN: 3460

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.72
PhyloP100		-0.49
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: rs3775318; hg19: chr4-166254353;