Genetic Variant YRDC:p.Val120Leu (chr1-37807823-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024640.4(YRDC):c.358G>C(p.Val120Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000464 in 1,509,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

YRDC
NM_024640.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20737672).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YRDC	NM_024640.4 link	c.358G>C	p.Val120Leu	missense_variant	Exon 1 of 5	ENST00000373044.3	NP_078916.3	Q86U90
C1orf122	NM_198446.3 link	c.-582C>G		5_prime_UTR_variant	Exon 1 of 3	ENST00000373042.5	NP_940848.2	Q6ZSJ8-1
C1orf122	NM_001142726.2 link	c.-638C>G		5_prime_UTR_variant	Exon 1 of 3		NP_001136198.1	Q6ZSJ8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YRDC	ENST00000373044.3 link	c.358G>C	p.Val120Leu	missense_variant	Exon 1 of 5	1	NM_024640.4	ENSP00000362135.2		Q86U90
C1orf122	ENST00000373042 link	c.-582C>G		5_prime_UTR_variant	Exon 1 of 3	1	NM_198446.3	ENSP00000362133.4		Q6ZSJ8-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000178

AC:

AN:

112272

Hom.:

AF XY:

0.00

AC XY:

AN XY:

62330

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000446

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000244

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000464

AC:

AN:

1357588

Hom.:

Cov.:

AF XY:

0.0000478

AC XY:

AN XY:

669666

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000297

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000544

Gnomad4 OTH exome

AF:

0.0000711

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000517

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Jul 21, 2022

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

Eigen

Benign

-0.11

Eigen_PC

Benign

0.037

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.86

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.88

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.30

Sift

Benign

0.062

Sift4G

Uncertain

0.057

Polyphen

0.058

Vest4

0.36

MutPred

0.61

Loss of methylation at K116 (P = 0.0754);

MVP

0.20

MPC

0.28

ClinPred

0.32

GERP RS

4.9

Varity_R

0.22

gMVP

0.58

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over