Variant 5-53109714-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The ENST00000450852.8(MOCS2):c.16C>A(p.Gln6Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,400,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q6R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

MOCS2
ENST00000450852.8 missense, splice_region

Scores

Splicing: ADA: 0.1497

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.60

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1

In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 5 uncertain in ENST00000450852.8

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.42372668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOCS2	NM_176806.4 linkuse as main transcript	c.16C>A	p.Gln6Lys	missense_variant, splice_region_variant	1/7	ENST00000450852.8	NP_789776.1
MOCS2	NM_004531.5 linkuse as main transcript	c.-633C>A		5_prime_UTR_variant	1/7	ENST00000396954.8	NP_004522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOCS2	ENST00000450852.8 linkuse as main transcript	c.16C>A	p.Gln6Lys	missense_variant, splice_region_variant	1/7	1	NM_176806.4	ENSP00000411022
MOCS2	ENST00000396954.8 linkuse as main transcript	c.-633C>A		5_prime_UTR_variant	1/7	1	NM_004531.5	ENSP00000380157	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.14e-7

AC:

AN:

1400304

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690916

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000397

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.085

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.011

T;T;T;T;T;T

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.45

.;.;.;.;.;T

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.42

T;T;T;T;T;T

MetaSVM

Benign

-0.85

MutationTaster

Benign

1.0

D;N;N;N;N;N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.62

N;N;N;N;.;.

REVEL

Benign

0.26

Sift

Benign

0.17

T;T;T;T;.;.

Sift4G

Benign

0.79

T;T;T;T;T;T

Polyphen

0.92

P;P;P;P;P;P

Vest4

0.52

MutPred

0.45

Gain of methylation at Q6 (P = 9e-04);Gain of methylation at Q6 (P = 9e-04);Gain of methylation at Q6 (P = 9e-04);Gain of methylation at Q6 (P = 9e-04);Gain of methylation at Q6 (P = 9e-04);Gain of methylation at Q6 (P = 9e-04);

MVP

0.71

ClinPred

0.55

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.15

dbscSNV1_RF

Benign

0.24

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over