Variant chr5-53108643-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_176806.4(MOCS2):c.19G>T(p.Val7Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MOCS2
NM_176806.4 missense, splice_region

Scores

Splicing: ADA: 0.4072

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.72

Variant links:

Genes affected

MOCS2 (HGNC:7193): (molybdenum cofactor synthesis 2) Eukaryotic molybdoenzymes use a unique molybdenum cofactor (MoCo) consisting of a pterin, termed molybdopterin, and the catalytically active metal molybdenum. MoCo is synthesized from precursor Z by the heterodimeric enzyme molybdopterin synthase. The large and small subunits of molybdopterin synthase are both encoded from this gene by overlapping open reading frames. The proteins were initially thought to be encoded from a bicistronic transcript. They are now thought to be encoded from monocistronic transcripts. Alternatively spliced transcripts have been found for this locus that encode the large and small subunits. [provided by RefSeq, Jul 2008]

MOCS2 links:

MOCS2 (HGNC:):

MOCS2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.982

PP5

Variant 5-53108643-C-A is Pathogenic according to our data. Variant chr5-53108643-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 6114.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-53108643-C-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOCS2	NM_004531.5 linkuse as main transcript	c.-169G>T		splice_region_variant	2/7	ENST00000396954.8	NP_004522.1	O96007A0A024QZS1
MOCS2	NM_176806.4 linkuse as main transcript	c.19G>T	p.Val7Phe	missense_variant, splice_region_variant	2/7	ENST00000450852.8	NP_789776.1	O96033
MOCS2	NM_004531.5 linkuse as main transcript	c.-169G>T		5_prime_UTR_variant	2/7	ENST00000396954.8	NP_004522.1	O96007A0A024QZS1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MOCS2	ENST00000396954.8 linkuse as main transcript	c.-169G>T		splice_region_variant	2/7	1	NM_004531.5	ENSP00000380157.3	O96007
MOCS2	ENST00000450852.8 linkuse as main transcript	c.19G>T	p.Val7Phe	missense_variant, splice_region_variant	2/7	1	NM_176806.4	ENSP00000411022.3	O96033
MOCS2	ENST00000396954.8 linkuse as main transcript	c.-169G>T		5_prime_UTR_variant	2/7	1	NM_004531.5	ENSP00000380157.3	O96007

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000405

AC:

AN:

246906

Hom.:

AF XY:

0.00000746

AC XY:

AN XY:

134038

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000560

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1459652

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725944

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 11, 2003

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;T;T;T;T;T;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.48

.;.;.;.;.;T;T

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.98

D;D;D;D;D;D;D

MetaSVM

Benign

-0.59

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.4

N;N;N;N;.;.;.

REVEL

Uncertain

0.59

Sift

Uncertain

0.0060

D;D;D;D;.;.;.

Sift4G

Uncertain

0.012

D;D;D;D;D;D;D

Polyphen

0.95

P;P;P;P;P;P;.

Vest4

0.82

MutPred

0.82

Loss of disorder (P = 0.1364);Loss of disorder (P = 0.1364);Loss of disorder (P = 0.1364);Loss of disorder (P = 0.1364);Loss of disorder (P = 0.1364);Loss of disorder (P = 0.1364);.;

MVP

0.77

ClinPred

0.37

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.41

dbscSNV1_RF

Benign

0.52

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.29

Position offset: 0

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