rs1367687550

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014484.5(MOCS3):​c.71T>A​(p.Leu24Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. L24P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

MOCS3
NM_014484.5 missense

Scores

2
8
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.88
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]
DPM1 (HGNC:3005): (dolichyl-phosphate mannosyltransferase subunit 1, catalytic) Dolichol-phosphate mannose (Dol-P-Man) serves as a donor of mannosyl residues on the lumenal side of the endoplasmic reticulum (ER). Lack of Dol-P-Man results in defective surface expression of GPI-anchored proteins. Dol-P-Man is synthesized from GDP-mannose and dolichol-phosphate on the cytosolic side of the ER by the enzyme dolichyl-phosphate mannosyltransferase. Human DPM1 lacks a carboxy-terminal transmembrane domain and signal sequence and is regulated by DPM2. Mutations in this gene are associated with congenital disorder of glycosylation type Ie. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MOCS3NM_014484.5 linkc.71T>A p.Leu24Gln missense_variant Exon 1 of 1 ENST00000244051.3 NP_055299.1 O95396

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MOCS3ENST00000244051.3 linkc.71T>A p.Leu24Gln missense_variant Exon 1 of 1 6 NM_014484.5 ENSP00000244051.1 O95396
DPM1ENST00000683466.1 linkc.-327A>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 8 ENSP00000507404.1 A0A804HJ93
DPM1ENST00000683466.1 linkc.-327A>T 5_prime_UTR_variant Exon 1 of 8 ENSP00000507404.1 A0A804HJ93

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.050
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.37
T
Eigen
Benign
0.037
Eigen_PC
Benign
-0.14
FATHMM_MKL
Benign
0.20
N
LIST_S2
Benign
0.76
T
M_CAP
Uncertain
0.22
D
MetaRNN
Uncertain
0.60
D
MetaSVM
Benign
-0.47
T
MutationAssessor
Pathogenic
3.2
M
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-1.4
N
REVEL
Uncertain
0.41
Sift
Uncertain
0.013
D
Sift4G
Uncertain
0.041
D
Polyphen
0.99
D
Vest4
0.46
MutPred
0.22
Loss of stability (P = 0.0095);
MVP
0.93
MPC
1.3
ClinPred
0.96
D
GERP RS
3.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.39
gMVP
0.78

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1367687550; hg19: chr20-49575450; API