rs17585739

Variant names:

• chr4-165341895-G-A
• rs17585739
• NM_006745.5:c.831G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006745.5(MSMO1):​c.831G>A​(p.Gln277Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0603 in 1,612,140 control chromosomes in the GnomAD database, including 3,225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.062 (342 hom., cov: 32)
  • Exomes 𝑓: 0.060 (2883 hom.)
• Consequence: MSMO1 NM_006745.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.174
• Publications: 11 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000309940 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 4-165341895-G-A is Benign according to our data. Variant chr4-165341895-G-A is described in ClinVar as Benign. ClinVar VariationId is 1229277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.174 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0744 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSMO1	NM_006745.5	MANE Select	c.831G>A	p.Gln277Gln	synonymous	Exon 6 of 6	NP_006736.1
	MSMO1	NM_001440534.1		c.831G>A	p.Gln277Gln	synonymous	Exon 6 of 6	NP_001427463.1
	MSMO1	NM_001017369.3		c.438G>A	p.Gln146Gln	synonymous	Exon 5 of 5	NP_001017369.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSMO1	ENST00000261507.11	TSL:1 MANE Select	c.831G>A	p.Gln277Gln	synonymous	Exon 6 of 6	ENSP00000261507.6
	MSMO1	ENST00000393766.6	TSL:2	c.438G>A	p.Gln146Gln	synonymous	Exon 5 of 5	ENSP00000377361.2
	ENSG00000309940	ENST00000846052.1		n.242C>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0621 AC: 9434 AN: 151990 Hom.: 342 Cov.: 32

Gnomad AFR AF: 0.0766

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0340

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0445

Gnomad FIN AF: 0.0974

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0625

Gnomad OTH AF: 0.0532

GnomAD2 exomes AF: 0.0534 AC: 13409 AN: 251196 AF XY: 0.0534

Gnomad AFR exome AF: 0.0769

Gnomad AMR exome AF: 0.0236

Gnomad ASJ exome AF: 0.0373

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0873

Gnomad NFE exome AF: 0.0637

Gnomad OTH exome AF: 0.0523

GnomAD4 exome AF: 0.0601 AC: 87787 AN: 1460032 Hom.: 2883 Cov.: 30 AF XY: 0.0596 AC XY: 43322 AN XY: 726428

African (AFR) AF: 0.0788 AC: 2634 AN: 33428

American (AMR) AF: 0.0255 AC: 1141 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0371 AC: 969 AN: 26116

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39610

South Asian (SAS) AF: 0.0506 AC: 4366 AN: 86214

European-Finnish (FIN) AF: 0.0858 AC: 4585 AN: 53410

Middle Eastern (MID) AF: 0.0175 AC: 100 AN: 5704

European-Non Finnish (NFE) AF: 0.0636 AC: 70606 AN: 1110498

Other (OTH) AF: 0.0560 AC: 3376 AN: 60330

GnomAD4 genome AF: 0.0621 AC: 9450 AN: 152108 Hom.: 342 Cov.: 32 AF XY: 0.0624 AC XY: 4639 AN XY: 74348

African (AFR) AF: 0.0766 AC: 3179 AN: 41480

American (AMR) AF: 0.0340 AC: 519 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0357 AC: 124 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5180

South Asian (SAS) AF: 0.0441 AC: 213 AN: 4828

European-Finnish (FIN) AF: 0.0974 AC: 1029 AN: 10568

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0626 AC: 4253 AN: 67982

Other (OTH) AF: 0.0559 AC: 118 AN: 2110

Alfa AF: 0.0613 Hom.: 204

Bravo AF: 0.0578

Asia WGS AF: 0.0460 AC: 160 AN: 3476

EpiCase AF: 0.0546

EpiControl AF: 0.0568

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	MSMO1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	1.0
DANN	Benign	0.41
PhyloP100		0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs17585739; hg19: chr4-166263047; COSMIC: COSV54971269; COSMIC: COSV54971269;