Genetic Variant YRDC:p.Glu158Gly (chr1-37807132-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024640.4(YRDC):c.473A>G(p.Glu158Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. E158E) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

YRDC
NM_024640.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0890

Publications

0 publications found

Variant links:

Genes affected

YRDC (HGNC:28905): (yrdC N6-threonylcarbamoyltransferase domain containing) Predicted to enable nucleotidyltransferase activity and tRNA binding activity. Acts upstream of or within negative regulation of transport. Predicted to be located in membrane and mitochondrion. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

YRDC links:

C1orf122 (HGNC:24789): (chromosome 1 open reading frame 122)

C1orf122 links:

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ACMG classification

Classification was made for transcript

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=0.11698899).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024640.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YRDC	NM_024640.4	MANE Select	c.473A>G	p.Glu158Gly	missense	Exon 2 of 5	NP_078916.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
YRDC	ENST00000373044.3	TSL:1 MANE Select	c.473A>G	p.Glu158Gly	missense	Exon 2 of 5	ENSP00000362135.2	Q86U90
C1orf122	ENST00000373043.1	TSL:1	c.-1553T>C		5_prime_UTR	Exon 1 of 2	ENSP00000362134.1	Q6ZSJ8-2
YRDC	ENST00000882854.1		c.473A>G	p.Glu158Gly	missense	Exon 2 of 5	ENSP00000552913.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000795

AC:

AN:

251438

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000150

AC:

AN:

1461822

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53368

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

1112000

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

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:

0.0000712

Hom.:

Bravo

AF:

0.0000151

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.79

M_CAP

Benign

0.030

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.99

PhyloP100

-0.089

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.035

Sift

Benign

0.27

Sift4G

Benign

0.27

Polyphen

0.12

Vest4

0.35

MutPred

0.44

Loss of solvent accessibility (P = 0.0387)

MVP

0.16

MPC

0.31

ClinPred

0.16

GERP RS

3.3

PromoterAI

-0.011

Neutral

(source)

Varity_R

0.13

gMVP

0.53

Mutation Taster

=289/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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