Genetic Variant NM_024640.4:c.247G>A (chr1-37807934-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024640.4(YRDC):c.247G>A(p.Val83Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000241 in 1,245,184 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 9.1e-7 ( 0 hom. )

Consequence

YRDC
NM_024640.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.90

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.247G>A	p.Val83Met	missense	Exon 1 of 5	NP_078916.3
C1orf122	NM_198446.3	MANE Select	c.-471C>T		5_prime_UTR	Exon 1 of 3	NP_940848.2	Q6ZSJ8-1
C1orf122	NM_001142726.2		c.-527C>T		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.247G>A	p.Val83Met	missense	Exon 1 of 5	ENSP00000362135.2	Q86U90
C1orf122	ENST00000373042.5	TSL:1 MANE Select	c.-471C>T		5_prime_UTR	Exon 1 of 3	ENSP00000362133.4	Q6ZSJ8-1
C1orf122	ENST00000373043.1	TSL:1	c.-751C>T		5_prime_UTR	Exon 1 of 2	ENSP00000362134.1	Q6ZSJ8-2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000660

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

5840

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00

GnomAD4 exome

AF:

9.14e-7

AC:

AN:

1094040

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

520244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22924

American (AMR)

AF:

0.000114

AC:

AN:

8736

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14794

East Asian (EAS)

AF:

0.00

AC:

AN:

26404

South Asian (SAS)

AF:

0.00

AC:

AN:

25830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21904

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2974

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

926558

Other (OTH)

AF:

0.00

AC:

AN:

43916

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.0000132

AC:

AN:

151144

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73870

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41410

American (AMR)

AF:

0.0000659

AC:

AN:

15180

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5110

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10198

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67676

Other (OTH)

AF:

0.00

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.00

Hom.:

Bravo

AF:

0.0000453

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

Pathogenic

0.79

BayesDel_addAF

Uncertain

0.051

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.62

LIST_S2

Uncertain

0.97

M_CAP

Pathogenic

0.75

MetaRNN

Uncertain

0.55

MetaSVM

Benign

-0.32

MutationAssessor

Pathogenic

3.4

PhyloP100

2.9

PrimateAI

Pathogenic

0.97

PROVEAN

Benign

-2.0

REVEL

Benign

0.22

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0040

Polyphen

0.26

Vest4

0.48

MutPred

0.72

Loss of sheet (P = 0.0457)

MVP

0.18

MPC

0.68

ClinPred

0.96

GERP RS

2.6

PromoterAI

0.31

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.27

gMVP

0.79

Mutation Taster

=73/27

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