Genetic Variant NM_024640.4:c.358G>C (chr1-37807823-C-G) – 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.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

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:

Genome browser will be placed here

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=0.20737672).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
YRDC	NM_024640.4	MANE Select	c.358G>C	p.Val120Leu	missense	Exon 1 of 5	NP_078916.3
C1orf122	NM_198446.3	MANE Select	c.-582C>G		5_prime_UTR	Exon 1 of 3	NP_940848.2	Q6ZSJ8-1
C1orf122	NM_001142726.2		c.-638C>G		5_prime_UTR	Exon 1 of 3	NP_001136198.1	Q6ZSJ8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
YRDC	ENST00000373044.3	TSL:1 MANE Select	c.358G>C	p.Val120Leu	missense	Exon 1 of 5	ENSP00000362135.2	Q86U90
C1orf122	ENST00000373042.5	TSL:1 MANE Select	c.-582C>G		5_prime_UTR	Exon 1 of 3	ENSP00000362133.4	Q6ZSJ8-1
C1orf122	ENST00000373043.1	TSL:1	c.-862C>G		5_prime_UTR	Exon 1 of 2	ENSP00000362134.1	Q6ZSJ8-2

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

GnomAD2 exomes

AF:

0.0000178

AC:

AN:

112272

AF XY:

0.00

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 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

African (AFR)

AF:

0.00

AC:

AN:

29242

American (AMR)

AF:

0.0000297

AC:

AN:

33684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24436

East Asian (EAS)

AF:

0.00

AC:

AN:

32890

South Asian (SAS)

AF:

0.00

AC:

AN:

78152

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33118

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3990

European-Non Finnish (NFE)

AF:

0.0000544

AC:

AN:

1065824

Other (OTH)

AF:

0.0000711

AC:

AN:

56252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

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

AF:

0.0000460

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41576

American (AMR)

AF:

0.00

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000517

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

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

PhyloP100

1.4

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

PromoterAI

0.031

Neutral

(source)

Varity_R

0.22

gMVP

0.58

Mutation Taster

=84/16

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over