4-165333821-A-G

Position:

• chr4-165333821-A-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.255+196A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 152,056 control chromosomes in the GnomAD database, including 24,791 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.57 (24791 hom., cov: 33)
• Consequence: MSMO1 NM_006745.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.109

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=-0.88).
• BP6: Variant 4-165333821-A-G is Benign according to our data. Variant chr4-165333821-A-G is described in ClinVar as [Benign]. Clinvar id is 1267620.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSMO1	NM_006745.5	c.255+196A>G		intron_variant		ENST00000261507.11	NP_006736.1
MSMO1	NM_001017369.3	c.-138-3968A>G		intron_variant			NP_001017369.1
MSMO1	XM_005263176.3	c.255+196A>G		intron_variant			XP_005263233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSMO1	ENST00000261507.11	c.255+196A>G		intron_variant		1	NM_006745.5	ENSP00000261507.6
MSMO1	ENST00000504317.1	c.255+196A>G		intron_variant		1		ENSP00000423633.1
MSMO1	ENST00000507013.5	c.255+196A>G		intron_variant		2		ENSP00000425241.1
MSMO1	ENST00000393766.6	c.-138-3968A>G		intron_variant		2		ENSP00000377361.2

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86273 AN: 151936 Hom.: 24761 Cov.: 33

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.574

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

GnomAD4 genome AF: 0.568 AC: 86364 AN: 152056 Hom.: 24791 Cov.: 33 AF XY: 0.571 AC XY: 42425 AN XY: 74334

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.586

Gnomad4 OTH AF: 0.574

Alfa AF: 0.577 Hom.: 5882

Bravo AF: 0.572

Asia WGS AF: 0.488 AC: 1696 AN: 3478

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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.0
DANN	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2118496; hg19: chr4-166254973;