Variant chr1-37807963-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_024640.4(YRDC):c.218C>A(p.Ala73Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000164 in 1,217,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 9.4e-7 ( 0 hom. )

Consequence

YRDC
NM_024640.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.86

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.772

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
YRDC	NM_024640.4 linkuse as main transcript	c.218C>A	p.Ala73Asp	missense_variant	1/5	ENST00000373044.3
C1orf122	NM_198446.3 linkuse as main transcript	c.-442G>T		5_prime_UTR_variant	1/3	ENST00000373042.5
C1orf122	NM_001142726.2 linkuse as main transcript	c.-498G>T		5_prime_UTR_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YRDC	ENST00000373044.3 linkuse as main transcript	c.218C>A	p.Ala73Asp	missense_variant	1/5	1	NM_024640.4	P1
C1orf122	ENST00000373042.5 linkuse as main transcript	c.-442G>T		5_prime_UTR_variant	1/3	1	NM_198446.3	P1	Q6ZSJ8-1

Frequencies

GnomAD3 genomes

AF:

0.00000666

AC:

AN:

150150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.37e-7

AC:

AN:

1067364

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

504668

show subpopulations

Gnomad4 AFR exome

AF:

0.0000450

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000666

AC:

AN:

150150

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73258

show subpopulations

Gnomad4 AFR

AF:

0.0000243

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.218C>A (p.A73D) alteration is located in exon 1 (coding exon 1) of the YRDC gene. This alteration results from a C to A substitution at nucleotide position 218, causing the alanine (A) at amino acid position 73 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.63

Eigen

Benign

0.055

Eigen_PC

Benign

0.055

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.66

M_CAP

Pathogenic

0.95

MetaRNN

Pathogenic

0.77

MetaSVM

Benign

-0.47

MutationAssessor

Pathogenic

4.5

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.95

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.24

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

0.022

Vest4

0.67

MutPred

0.62

Loss of MoRF binding (P = 0.0405);

MVP

0.17

MPC

1.1

ClinPred

1.0

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.84

gMVP

0.88

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