4-165337848-C-T

Variant names:

• chr4-165337848-C-T
• rs1304406584
• NM_006745.5:c.315C>T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_006745.5(MSMO1):​c.315C>T​(p.His105His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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: 0.0000027 (0 hom.)
• Consequence: MSMO1 NM_006745.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=1.3 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSMO1	NM_006745.5	c.315C>T	p.His105His	synonymous_variant	Exon 3 of 6	ENST00000261507.11	NP_006736.1
MSMO1	XM_005263176.3	c.315C>T	p.His105His	synonymous_variant	Exon 3 of 6		XP_005263233.1
MSMO1	NM_001017369.3	c.-79C>T		5_prime_UTR_variant	Exon 2 of 5		NP_001017369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSMO1	ENST00000261507.11	c.315C>T	p.His105His	synonymous_variant	Exon 3 of 6	1	NM_006745.5	ENSP00000261507.6
MSMO1	ENST00000504317.1	c.315C>T	p.His105His	synonymous_variant	Exon 3 of 5	1		ENSP00000423633.1
MSMO1	ENST00000507013.5	c.315C>T	p.His105His	synonymous_variant	Exon 3 of 5	2		ENSP00000425241.1
MSMO1	ENST00000393766	c.-79C>T		5_prime_UTR_variant	Exon 2 of 5	2		ENSP00000377361.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461074 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726902

Gnomad4 AFR exome AF: 0.000120

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	12
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1304406584; hg19: chr4-166259000;