chr5-53109714-G-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_176806.4(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. 15/21 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
NM_176806.4 missense, splice_region

Scores

Splicing: ADA: 0.1497

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.60

Publications

7 publications found

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-DT (HGNC:27417): (MOCS2 divergent transcript)

MOCS2-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176806.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MOCS2	NM_176806.4	MANE Plus Clinical	c.16C>A	p.Gln6Lys	missense splice_region	Exon 1 of 7	NP_789776.1	O96033
MOCS2	NM_004531.5	MANE Select	c.-633C>A		5_prime_UTR	Exon 1 of 7	NP_004522.1	O96007
MOCS2-DT	NR_034107.2		n.-128G>T		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MOCS2	ENST00000450852.8	TSL:1 MANE Plus Clinical	c.16C>A	p.Gln6Lys	missense splice_region	Exon 1 of 7	ENSP00000411022.3	O96033
MOCS2	ENST00000396954.8	TSL:1 MANE Select	c.-633C>A		5_prime_UTR	Exon 1 of 7	ENSP00000380157.3	O96007
MOCS2	ENST00000855414.1		c.-50C>A		splice_region	Exon 1 of 6	ENSP00000525473.1

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31598

American (AMR)

AF:

0.00

AC:

AN:

36230

Ashkenazi Jewish (ASJ)

AF:

0.0000397

AC:

AN:

25198

East Asian (EAS)

AF:

0.00

AC:

AN:

35816

South Asian (SAS)

AF:

0.00

AC:

AN:

79296

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5492

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1080022

Other (OTH)

AF:

0.00

AC:

AN:

58052

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Uncertain

0.085

BayesDel_noAF

Benign

-0.12

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.011

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.45

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.42

MetaSVM

Benign

-0.85

PhyloP100

2.6

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.62

REVEL

Benign

0.26

Sift

Benign

0.17

Sift4G

Benign

0.79

Polyphen

0.92

Vest4

0.52

MutPred

0.45

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

MVP

0.71

ClinPred

0.55

GERP RS

5.0

PromoterAI

0.12

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Mutation Taster

=68/32

polymorphism

(source)

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

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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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over