Variant rs7269297 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_014484.5(MOCS3):c.1285T>G(p.Ser429Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,614,230 control chromosomes in the GnomAD database, including 125 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.0065 ( 4 hom., cov: 33)

Exomes 𝑓: 0.011 ( 121 hom. )

Consequence

MOCS3
NM_014484.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.00300

Variant links:

Genes affected

MOCS3 (HGNC:15765): (molybdenum cofactor synthesis 3) Molybdenum cofactor (MoCo) is necessary for the function of all molybdoenzymes. The protein encoded by this gene adenylates and activates molybdopterin synthase, an enzyme required for biosynthesis of MoCo. This gene contains no introns. A pseudogene of this gene is present on chromosome 14. [provided by RefSeq, Nov 2012]

MOCS3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028296113).

BP6

Variant 20-50960127-T-G is Benign according to our data. Variant chr20-50960127-T-G is described in ClinVar as [Benign]. Clinvar id is 1166025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOCS3	NM_014484.5 linkuse as main transcript	c.1285T>G	p.Ser429Ala	missense_variant	1/1	ENST00000244051.3	NP_055299.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOCS3	ENST00000244051.3 linkuse as main transcript	c.1285T>G	p.Ser429Ala	missense_variant	1/1		NM_014484.5	ENSP00000244051	P1

Frequencies

GnomAD3 genomes

AF:

0.00655

AC:

997

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00198

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0117

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00630

AC:

1584

AN:

251436

Hom.:

AF XY:

0.00678

AC XY:

922

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00523

Gnomad FIN exome

AF:

0.00323

Gnomad NFE exome

AF:

0.0109

Gnomad OTH exome

AF:

0.00619

GnomAD4 exome

AF:

0.0107

AC:

15599

AN:

1461890

Hom.:

121

Cov.:

AF XY:

0.0106

AC XY:

7676

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00155

Gnomad4 AMR exome

AF:

0.00161

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00486

Gnomad4 FIN exome

AF:

0.00367

Gnomad4 NFE exome

AF:

0.0128

Gnomad4 OTH exome

AF:

0.00934

GnomAD4 genome

AF:

0.00654

AC:

996

AN:

152340

Hom.:

Cov.:

AF XY:

0.00595

AC XY:

443

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00197

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00393

Gnomad4 FIN

AF:

0.00311

Gnomad4 NFE

AF:

0.0117

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00985

Hom.:

Bravo

AF:

0.00643

TwinsUK

AF:

0.0135

AC:

ALSPAC

AF:

0.0132

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.0115

AC:

ExAC

AF:

0.00626

AC:

760

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0103

EpiControl

AF:

0.0105

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 29, 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

0.061

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.50

DANN

Benign

0.52

DEOGEN2

Benign

0.092

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.19

MetaRNN

Benign

0.0028

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.98

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.21

REVEL

Benign

0.022

Sift

Benign

0.57

Sift4G

Benign

0.65

Polyphen

0.0

Vest4

0.033

MVP

0.26

MPC

0.44

ClinPred

0.0027

GERP RS

-5.6

Varity_R

0.069

gMVP

0.33

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

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