4-165333022-C-G

Position:

• chr4-165333022-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSMO1	NM_006745.5	c.-31-318C>G		intron_variant		ENST00000261507.11	NP_006736.1
MSMO1	NM_001017369.3	c.-138-4767C>G		intron_variant			NP_001017369.1
MSMO1	XM_005263176.3	c.-31-318C>G		intron_variant			XP_005263233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSMO1	ENST00000261507.11	c.-31-318C>G		intron_variant		1	NM_006745.5	ENSP00000261507	P1

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

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.292

Alfa AF: 0.270 Hom.: 762

Bravo AF: 0.269

Asia WGS AF: 0.425 AC: 1473 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.42
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs3775317; hg19: chr4-166254174;