4-165337753-G-A

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.256-36G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0565 in 1,605,226 control chromosomes in the GnomAD database, including 2,935 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.043 (205 hom., cov: 33)
  • Exomes 𝑓: 0.058 (2730 hom.)
• Consequence: MSMO1 NM_006745.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.267

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=-0.8).
• BP6: Variant 4-165337753-G-A is Benign according to our data. Variant chr4-165337753-G-A is described in ClinVar as [Benign]. Clinvar id is 1252181.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSMO1	NM_006745.5	c.256-36G>A		intron_variant		ENST00000261507.11
MSMO1	NM_001017369.3	c.-138-36G>A		intron_variant
MSMO1	XM_005263176.3	c.256-36G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSMO1	ENST00000261507.11	c.256-36G>A		intron_variant		1	NM_006745.5	P1
MSMO1	ENST00000504317.1	c.256-36G>A		intron_variant		1
MSMO1	ENST00000393766.6	c.-138-36G>A		intron_variant		2
MSMO1	ENST00000507013.5	c.256-36G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0429 AC: 6534 AN: 152190 Hom.: 205 Cov.: 33

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0251

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0445

Gnomad FIN AF: 0.0974

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0623

Gnomad OTH AF: 0.0340

GnomAD3 exomes AF: 0.0484 AC: 12106 AN: 250298 Hom.: 432 AF XY: 0.0496 AC XY: 6716 AN XY: 135312

Gnomad AFR exome AF: 0.00918

Gnomad AMR exome AF: 0.0207

Gnomad ASJ exome AF: 0.0374

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0498

Gnomad FIN exome AF: 0.0873

Gnomad NFE exome AF: 0.0634

Gnomad OTH exome AF: 0.0498

GnomAD4 exome AF: 0.0579 AC: 84170 AN: 1452918 Hom.: 2730 Cov.: 29 AF XY: 0.0577 AC XY: 41741 AN XY: 723382

Gnomad4 AFR exome AF: 0.00798

Gnomad4 AMR exome AF: 0.0218

Gnomad4 ASJ exome AF: 0.0369

Gnomad4 EAS exome AF: 0.000177

Gnomad4 SAS exome AF: 0.0504

Gnomad4 FIN exome AF: 0.0859

Gnomad4 NFE exome AF: 0.0633

Gnomad4 OTH exome AF: 0.0514

GnomAD4 genome AF: 0.0429 AC: 6533 AN: 152308 Hom.: 205 Cov.: 33 AF XY: 0.0440 AC XY: 3279 AN XY: 74476

Gnomad4 AFR AF: 0.0110

Gnomad4 AMR AF: 0.0250

Gnomad4 ASJ AF: 0.0357

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0441

Gnomad4 FIN AF: 0.0974

Gnomad4 NFE AF: 0.0623

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.0497 Hom.: 32

Bravo AF: 0.0353

Asia WGS AF: 0.0280 AC: 99 AN: 3476

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.1
Dann	Benign	0.77

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: rs72701627; hg19: chr4-166258905;