5-53108643-C-T

Variant names:

• chr5-53108643-C-T
• rs121908608
• NM_004531.5:c.-169G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004531.5(MOCS2):​c.-169G>A variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MOCS2 NM_004531.5 splice_region
• Scores: Splicing: ADA: 0.002664
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.72
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• sulfite oxidase deficiency due to molybdenum cofactor deficiency type B

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1547868).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOCS2	NM_004531.5	c.-169G>A		splice_region_variant	Exon 2 of 7	ENST00000396954.8	NP_004522.1
MOCS2	NM_176806.4	c.19G>A	p.Val7Ile	missense_variant, splice_region_variant	Exon 2 of 7	ENST00000450852.8	NP_789776.1
MOCS2	NM_004531.5	c.-169G>A		5_prime_UTR_variant	Exon 2 of 7	ENST00000396954.8	NP_004522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOCS2	ENST00000396954.8	c.-169G>A		splice_region_variant	Exon 2 of 7	1	NM_004531.5	ENSP00000380157.3
MOCS2	ENST00000450852.8	c.19G>A	p.Val7Ile	missense_variant, splice_region_variant	Exon 2 of 7	1	NM_176806.4	ENSP00000411022.3
MOCS2	ENST00000396954.8	c.-169G>A		5_prime_UTR_variant	Exon 2 of 7	1	NM_004531.5	ENSP00000380157.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459652 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725944

African (AFR) AF: 0.0000299 AC: 1 AN: 33436

American (AMR) AF: 0.00 AC: 0 AN: 44304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39572

South Asian (SAS) AF: 0.00 AC: 0 AN: 85640

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111240

Other (OTH) AF: 0.00 AC: 0 AN: 60314

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.011	T;T;T;T;T;T;T
Eigen	Benign	-0.023
Eigen_PC	Benign	-0.029
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.41	.;.;.;.;.;T;T
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.15	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		2.7
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.090	N;N;N;N;.;.;.
REVEL	Benign	0.11
Sift	Benign	0.31	T;T;T;T;.;.;.
Sift4G	Benign	0.33	T;T;T;T;T;T;T
Polyphen		0.018	B;B;B;B;B;B;.
Vest4		0.17
MutPred		0.59		Loss of disorder (P = 0.1105);Loss of disorder (P = 0.1105);Loss of disorder (P = 0.1105);Loss of disorder (P = 0.1105);Loss of disorder (P = 0.1105);Loss of disorder (P = 0.1105);.;
MVP		0.46
ClinPred		0.11	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=55/45	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0027
dbscSNV1_RF	Benign	0.19
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs121908608; hg19: chr5-52404473;