NM_024640.4:c.244G>T

Variant names:

• chr1-37807937-C-A
• rs768654643
• NM_024640.4:c.244G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024640.4(YRDC):​c.244G>T​(p.Val82Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 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. V82V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: YRDC NM_024640.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.538

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]

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

ACMG classification

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=0.19413963).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YRDC	NM_024640.4	c.244G>T	p.Val82Leu	missense_variant	Exon 1 of 5	ENST00000373044.3	NP_078916.3
C1orf122	NM_198446.3	c.-468C>A		5_prime_UTR_variant	Exon 1 of 3	ENST00000373042.5	NP_940848.2
C1orf122	NM_001142726.2	c.-524C>A		5_prime_UTR_variant	Exon 1 of 3		NP_001136198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YRDC	ENST00000373044.3	c.244G>T	p.Val82Leu	missense_variant	Exon 1 of 5	1	NM_024640.4	ENSP00000362135.2
C1orf122	ENST00000373042	c.-468C>A		5_prime_UTR_variant	Exon 1 of 3	1	NM_198446.3	ENSP00000362133.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1087218 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 515976

Gnomad4 AFR exome AF: 0.00

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 Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.244G>T (p.V82L) alteration is located in exon 1 (coding exon 1) of the YRDC gene. This alteration results from a G to T substitution at nucleotide position 244, causing the valine (V) at amino acid position 82 to be replaced by a leucine (L). 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	Benign	0.33
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Benign	0.90
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.82	T
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.41	N
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.067
Sift	Benign	0.14	T
Sift4G	Benign	0.14	T
Polyphen		0.026	B
Vest4		0.12
MutPred		0.66		Loss of catalytic residue at V82 (P = 0.0297);
MVP		0.072
MPC		0.32
ClinPred		0.21	T
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		3.2
Varity_R		0.28
gMVP		0.60

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

Other links and lift over

dbSNP: rs768654643; hg19: chr1-38273609;