chr20-50958863-A-C

Position:

• chr20-50958863-A-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_014484.5(MOCS3):​c.21A>C​(p.Val7=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,595,124 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00070 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (2 hom.)
• Consequence: MOCS3 NM_014484.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -5.56

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 20-50958863-A-C is Benign according to our data. Variant chr20-50958863-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1092009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.56 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOCS3	NM_014484.5	c.21A>C	p.Val7=	synonymous_variant	1/1	ENST00000244051.3	NP_055299.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOCS3	ENST00000244051.3	c.21A>C	p.Val7=	synonymous_variant	1/1		NM_014484.5	ENSP00000244051	P1
DPM1	ENST00000683466.1	c.-277T>G		5_prime_UTR_variant	1/8			ENSP00000507404

Frequencies

GnomAD3 genomes AF: 0.000697 AC: 106 AN: 152108 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00103

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000532 AC: 130 AN: 244186 Hom.: 0 AF XY: 0.000518 AC XY: 69 AN XY: 133128

Gnomad AFR exome AF: 0.0000656

Gnomad AMR exome AF: 0.0000592

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000332

Gnomad FIN exome AF: 0.000558

Gnomad NFE exome AF: 0.00100

Gnomad OTH exome AF: 0.000671

GnomAD4 exome AF: 0.00118 AC: 1696 AN: 1442898 Hom.: 2 Cov.: 32 AF XY: 0.00108 AC XY: 768 AN XY: 713926

Gnomad4 AFR exome AF: 0.000182

Gnomad4 AMR exome AF: 0.0000685

Gnomad4 ASJ exome AF: 0.0000774

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.000518

Gnomad4 NFE exome AF: 0.00148

Gnomad4 OTH exome AF: 0.000589

GnomAD4 genome AF: 0.000696 AC: 106 AN: 152226 Hom.: 0 Cov.: 33 AF XY: 0.000430 AC XY: 32 AN XY: 74430

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000378

Gnomad4 NFE AF: 0.00103

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000819 Hom.: 0

Bravo AF: 0.000635

EpiCase AF: 0.000709

EpiControl AF: 0.00107

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 30, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	MOCS3: BP4, BP7 -

MOCS3-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 07, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.015
DANN	Benign	0.51

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

Other links and lift over

dbSNP: rs45500701; hg19: chr20-49575400;