NM_006745.5:c.731A>C

Variant names:

• chr4-165341795-A-C
• rs760048191
• NM_006745.5:c.731A>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006745.5(MSMO1):​c.731A>C​(p.Tyr244Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MSMO1 NM_006745.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.09

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.906

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSMO1	NM_006745.5	c.731A>C	p.Tyr244Ser	missense_variant	Exon 6 of 6	ENST00000261507.11	NP_006736.1
MSMO1	NM_001017369.3	c.338A>C	p.Tyr113Ser	missense_variant	Exon 5 of 5		NP_001017369.1
MSMO1	XM_005263176.3	c.731A>C	p.Tyr244Ser	missense_variant	Exon 6 of 6		XP_005263233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSMO1	ENST00000261507.11	c.731A>C	p.Tyr244Ser	missense_variant	Exon 6 of 6	1	NM_006745.5	ENSP00000261507.6
MSMO1	ENST00000393766.6	c.338A>C	p.Tyr113Ser	missense_variant	Exon 5 of 5	2		ENSP00000377361.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461286 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726998

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.61	D;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Uncertain	0.29	D
MutationAssessor	Benign	1.4	L;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-5.9	D;D
REVEL	Pathogenic	0.75
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;.
Vest4		0.87
MutPred		0.69		Gain of disorder (P = 0.0033);.;
MVP		0.81
MPC		1.2
ClinPred		0.99	D
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.90
gMVP		0.94

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: rs760048191; hg19: chr4-166262947;