Genetic Variant MOCS3:p.Ser429Ala (chr20-50960127-T-G) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S429L) has been classified as Uncertain significance.

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

Publications

13 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 1166025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014484.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOCS3	NM_014484.5	MANE Select	c.1285T>G	p.Ser429Ala	missense	Exon 1 of 1	NP_055299.1	O95396

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOCS3	ENST00000244051.3	TSL:6 MANE Select	c.1285T>G	p.Ser429Ala	missense	Exon 1 of 1	ENSP00000244051.1	O95396

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

GnomAD2 exomes

AF:

0.00630

AC:

1584

AN:

251436

AF XY:

0.00678

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 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

African (AFR)

AF:

0.00155

AC:

AN:

33480

American (AMR)

AF:

0.00161

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00486

AC:

419

AN:

86258

European-Finnish (FIN)

AF:

0.00367

AC:

196

AN:

53418

Middle Eastern (MID)

AF:

0.00277

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0128

AC:

14278

AN:

1112010

Other (OTH)

AF:

0.00934

AC:

564

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

1005

2010

3014

4019

5024

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

560

1120

1680

2240

2800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00654

AC:

996

AN:

152340

Hom.:

Cov.:

AF XY:

0.00595

AC XY:

443

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.00197

AC:

AN:

41588

American (AMR)

AF:

0.00216

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00393

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00311

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0117

AC:

798

AN:

68030

Other (OTH)

AF:

0.00332

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

110

164

219

274

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00953

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.50

(source)

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

PhyloP100

-0.0030

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

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over