rs7269297

Positions:

• chr20-50960127-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_014484.5(MOCS3):​c.1285T>G​(p.Ser429Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,614,230 control chromosomes in the GnomAD database, including 125 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S429L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0065 (4 hom., cov: 33)
  • Exomes 𝑓: 0.011 (121 hom.)
• Consequence: MOCS3 NM_014484.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00300

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028296113).
• BP6: Variant 20-50960127-T-G is Benign according to our data. Variant chr20-50960127-T-G is described in ClinVar as [Benign]. Clinvar id is 1166025.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOCS3	NM_014484.5	c.1285T>G	p.Ser429Ala	missense_variant	1/1	ENST00000244051.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOCS3	ENST00000244051.3	c.1285T>G	p.Ser429Ala	missense_variant	1/1		NM_014484.5	P1

Frequencies

GnomAD3 genomes AF: 0.00655 AC: 997 AN: 152222 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00198

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0117

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00630 AC: 1584 AN: 251436 Hom.: 7 AF XY: 0.00678 AC XY: 922 AN XY: 135906

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00523

Gnomad FIN exome AF: 0.00323

Gnomad NFE exome AF: 0.0109

Gnomad OTH exome AF: 0.00619

GnomAD4 exome AF: 0.0107 AC: 15599 AN: 1461890 Hom.: 121 Cov.: 32 AF XY: 0.0106 AC XY: 7676 AN XY: 727244

Gnomad4 AFR exome AF: 0.00155

Gnomad4 AMR exome AF: 0.00161

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00486

Gnomad4 FIN exome AF: 0.00367

Gnomad4 NFE exome AF: 0.0128

Gnomad4 OTH exome AF: 0.00934

GnomAD4 genome AF: 0.00654 AC: 996 AN: 152340 Hom.: 4 Cov.: 33 AF XY: 0.00595 AC XY: 443 AN XY: 74492

Gnomad4 AFR AF: 0.00197

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00393

Gnomad4 FIN AF: 0.00311

Gnomad4 NFE AF: 0.0117

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00985 Hom.: 24

Bravo AF: 0.00643

TwinsUK AF: 0.0135 AC: 50

ALSPAC AF: 0.0132 AC: 51

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.0115 AC: 99

ExAC AF: 0.00626 AC: 760

Asia WGS AF: 0.00346 AC: 13 AN: 3478

EpiCase AF: 0.0103

EpiControl AF: 0.0105

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.50
DANN	Benign	0.52
DEOGEN2	Benign	0.092	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.19	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.98	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.022
Sift	Benign	0.57	T
Sift4G	Benign	0.65	T
Polyphen		0.0	B
Vest4		0.033
MVP		0.26
MPC		0.44
ClinPred		0.0027	T
GERP RS		-5.6
Varity_R		0.069
gMVP		0.33

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: rs7269297; hg19: chr20-49576664; COSMIC: COSV99056501; COSMIC: COSV99056501;