NM_024640.4:c.290C>T

Variant names:

• chr1-37807891-G-A
• rs1370523074
• NM_024640.4:c.290C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_024640.4(YRDC):​c.290C>T​(p.Ala97Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000242 in 1,448,676 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 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: YRDC NM_024640.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.20
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.855

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YRDC	NM_024640.4	MANE Select	c.290C>T	p.Ala97Val	missense	Exon 1 of 5	NP_078916.3
	C1orf122	NM_198446.3	MANE Select	c.-514G>A		5_prime_UTR	Exon 1 of 3	NP_940848.2	Q6ZSJ8-1
	C1orf122	NM_001142726.2		c.-570G>A		5_prime_UTR	Exon 1 of 3	NP_001136198.1	Q6ZSJ8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YRDC	ENST00000373044.3	TSL:1 MANE Select	c.290C>T	p.Ala97Val	missense	Exon 1 of 5	ENSP00000362135.2	Q86U90
	C1orf122	ENST00000373042.5	TSL:1 MANE Select	c.-514G>A		5_prime_UTR	Exon 1 of 3	ENSP00000362133.4	Q6ZSJ8-1
	C1orf122	ENST00000373043.1	TSL:1	c.-794G>A		5_prime_UTR	Exon 1 of 2	ENSP00000362134.1	Q6ZSJ8-2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152004 Hom.: 0 Cov.: 33

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: 0.000284

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000268 AC: 2 AN: 74568 AF XY: 0.0000232

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: 0.000469

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000247 AC: 32 AN: 1296672 Hom.: 0 Cov.: 31 AF XY: 0.0000204 AC XY: 13 AN XY: 636682

African (AFR) AF: 0.00 AC: 0 AN: 26554

American (AMR) AF: 0.00 AC: 0 AN: 27774

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22636

East Asian (EAS) AF: 0.00 AC: 0 AN: 28698

South Asian (SAS) AF: 0.00 AC: 0 AN: 72422

European-Finnish (FIN) AF: 0.000785 AC: 25 AN: 31828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3800

European-Non Finnish (NFE) AF: 9.71e-7 AC: 1 AN: 1029928

Other (OTH) AF: 0.000113 AC: 6 AN: 53032

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152004 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74242

African (AFR) AF: 0.00 AC: 0 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.000284 AC: 3 AN: 10546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67958

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.82	T
M_CAP	Pathogenic	0.70	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.2
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.38
Sift	Benign	0.14	T
Sift4G	Uncertain	0.0060	D
Polyphen		0.92	P
Vest4		0.63
MutPred		0.74		Gain of loop (P = 0.069)
MVP		0.17
MPC		0.40
ClinPred		0.67	D
GERP RS		4.5
PromoterAI		0.097	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.46
gMVP		0.84
Mutation Taster		=61/39	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1370523074; hg19: chr1-38273563;