4-165337904-A-G

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.371A>G(p.Asn124Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00355 in 1,613,530 control chromosomes in the GnomAD database, including 174 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Synonymous variant affecting the same amino acid position (i.e. N124N) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.019 (91 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (83 hom.)
• Consequence: MSMO1 NM_006745.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.329

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 (MetaRNN=0.0022530258).
• BP6: Variant 4-165337904-A-G is Benign according to our data. Variant chr4-165337904-A-G is described in ClinVar as [Benign]. Clinvar id is 783431.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSMO1	NM_006745.5	c.371A>G	p.Asn124Ser	missense_variant	3/6	ENST00000261507.11
MSMO1	XM_005263176.3	c.371A>G	p.Asn124Ser	missense_variant	3/6
MSMO1	NM_001017369.3	c.-23A>G		5_prime_UTR_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSMO1	ENST00000261507.11	c.371A>G	p.Asn124Ser	missense_variant	3/6	1	NM_006745.5	P1
MSMO1	ENST00000504317.1	c.371A>G	p.Asn124Ser	missense_variant	3/5	1
MSMO1	ENST00000507013.5	c.371A>G	p.Asn124Ser	missense_variant	3/5	2
MSMO1	ENST00000393766.6	c.-23A>G		5_prime_UTR_variant	2/5	2

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 2880 AN: 152158 Hom.: 92 Cov.: 33

Gnomad AFR AF: 0.0649

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00858

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0177

GnomAD3 exomes AF: 0.00483 AC: 1213 AN: 250940 Hom.: 32 AF XY: 0.00355 AC XY: 482 AN XY: 135654

Gnomad AFR exome AF: 0.0675

Gnomad AMR exome AF: 0.00275

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000794

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00194 AC: 2838 AN: 1461254 Hom.: 83 Cov.: 31 AF XY: 0.00173 AC XY: 1259 AN XY: 726948

Gnomad4 AFR exome AF: 0.0701

Gnomad4 AMR exome AF: 0.00358

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000928

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000693

Gnomad4 OTH exome AF: 0.00389

GnomAD4 genome AF: 0.0190 AC: 2889 AN: 152276 Hom.: 91 Cov.: 33 AF XY: 0.0180 AC XY: 1342 AN XY: 74456

Gnomad4 AFR AF: 0.0649

Gnomad4 AMR AF: 0.00857

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0176

Alfa AF: 0.00898 Hom.: 21

Bravo AF: 0.0224

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0674 AC: 297

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00616 AC: 748

Asia WGS AF: 0.00260 AC: 9 AN: 3474

EpiCase AF: 0.000109

EpiControl AF: 0.00

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

Invitae

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	7.4
Dann	Uncertain	0.99
DEOGEN2	Benign	0.22	T;T;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.75	T;T;T
MetaRNN	Benign	0.0023	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.26	N;N;N
REVEL	Benign	0.067
Sift	Benign	0.18	T;T;T
Sift4G	Benign	0.25	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.24
MVP		0.25
MPC		0.24
ClinPred		0.0038	T
GERP RS		0.26
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.023
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs34499452; hg19: chr4-166259056;