chr4-165337904-A-G

Position:

chr4-165337904-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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.

Frequency

Genomes: 𝑓 0.019 ( 91 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 83 hom. )

Consequence

MSMO1
NM_006745.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.329

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein
MSMO1	NM_006745.5 linkuse as main transcript	c.371A>G	p.Asn124Ser	missense_variant	3/6	ENST00000261507.11	NP_006736.1
MSMO1	XM_005263176.3 linkuse as main transcript	c.371A>G	p.Asn124Ser	missense_variant	3/6		XP_005263233.1
MSMO1	NM_001017369.3 linkuse as main transcript	c.-23A>G		5_prime_UTR_variant	2/5		NP_001017369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSMO1	ENST00000261507.11 linkuse as main transcript	c.371A>G	p.Asn124Ser	missense_variant	3/6	1	NM_006745.5	ENSP00000261507	P1	Q15800-1
MSMO1	ENST00000504317.1 linkuse as main transcript	c.371A>G	p.Asn124Ser	missense_variant	3/5	1		ENSP00000423633
MSMO1	ENST00000507013.5 linkuse as main transcript	c.371A>G	p.Asn124Ser	missense_variant	3/5	2		ENSP00000425241
MSMO1	ENST00000393766.6 linkuse as main transcript	c.-23A>G		5_prime_UTR_variant	2/5	2		ENSP00000377361		Q15800-2

Frequencies

GnomAD3 genomes

AF:

0.0189

AC:

2880

AN:

152158

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00355

AC XY:

482

AN XY:

135654

show subpopulations

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.:

Cov.:

AF XY:

0.00173

AC XY:

1259

AN XY:

726948

show subpopulations

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.:

Cov.:

AF XY:

0.0180

AC XY:

1342

AN XY:

74456

show subpopulations

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.:

Bravo

AF:

0.0224

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0674

AC:

297

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00616

AC:

748

Asia WGS

AF:

0.00260

AC:

AN:

3474

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.59

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

LIST_S2

Benign

0.75

T;T;T

MetaRNN

Benign

0.0023

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.31

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over