4-165338009-C-T

Variant names:

• chr4-165338009-C-T
• rs12501541
• NM_006745.5:c.404+72C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006745.5(MSMO1):​c.404+72C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,375,948 control chromosomes in the GnomAD database, including 51,655 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5456 hom., cov: 32)
  • Exomes 𝑓: 0.26 (46199 hom.)
• Consequence: MSMO1 NM_006745.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0270

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-165338009-C-T is Benign according to our data. Variant chr4-165338009-C-T is described in ClinVar as [Benign]. Clinvar id is 1296795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSMO1	NM_006745.5	c.404+72C>T		intron_variant	Intron 3 of 5	ENST00000261507.11	NP_006736.1
MSMO1	NM_001017369.3	c.11+72C>T		intron_variant	Intron 2 of 4		NP_001017369.1
MSMO1	XM_005263176.3	c.404+72C>T		intron_variant	Intron 3 of 5		XP_005263233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSMO1	ENST00000261507.11	c.404+72C>T		intron_variant	Intron 3 of 5	1	NM_006745.5	ENSP00000261507.6
MSMO1	ENST00000504317.1	c.404+72C>T		intron_variant	Intron 3 of 4	1		ENSP00000423633.1
MSMO1	ENST00000507013.5	c.404+72C>T		intron_variant	Intron 3 of 4	2		ENSP00000425241.1
MSMO1	ENST00000393766.6	c.11+72C>T		intron_variant	Intron 2 of 4	2		ENSP00000377361.2

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37920 AN: 151792 Hom.: 5443 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.276

GnomAD4 exome AF: 0.261 AC: 318911 AN: 1224038 Hom.: 46199 AF XY: 0.265 AC XY: 163529 AN XY: 615962

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.528

Gnomad4 ASJ exome AF: 0.317

Gnomad4 EAS exome AF: 0.357

Gnomad4 SAS exome AF: 0.421

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.235

Gnomad4 OTH exome AF: 0.268

GnomAD4 genome AF: 0.250 AC: 37950 AN: 151910 Hom.: 5456 Cov.: 32 AF XY: 0.255 AC XY: 18936 AN XY: 74246

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.363

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.278

Alfa AF: 0.248 Hom.: 1140

Bravo AF: 0.263

Asia WGS AF: 0.413 AC: 1429 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.5
DANN	Benign	0.71
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: rs12501541; hg19: chr4-166259161; COSMIC: COSV54971198; COSMIC: COSV54971198;