rs1248910043

Variant names:

• chr1-37807880-C-G
• rs1248910043
• NM_024640.4:c.301G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024640.4(YRDC):​c.301G>C​(p.Ala101Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,458,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A101V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000084 (0 hom.)
• Consequence: YRDC NM_024640.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 3.04
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13436031).

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.301G>C	p.Ala101Pro	missense	Exon 1 of 5	NP_078916.3
	C1orf122	NM_198446.3	MANE Select	c.-525C>G		5_prime_UTR	Exon 1 of 3	NP_940848.2	Q6ZSJ8-1
	C1orf122	NM_001142726.2		c.-581C>G		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.301G>C	p.Ala101Pro	missense	Exon 1 of 5	ENSP00000362135.2	Q86U90
	C1orf122	ENST00000373042.5	TSL:1 MANE Select	c.-525C>G		5_prime_UTR	Exon 1 of 3	ENSP00000362133.4	Q6ZSJ8-1
	C1orf122	ENST00000373043.1	TSL:1	c.-805C>G		5_prime_UTR	Exon 1 of 2	ENSP00000362134.1	Q6ZSJ8-2

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152114 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.00000842 AC: 11 AN: 1306764 Hom.: 0 Cov.: 31 AF XY: 0.00000778 AC XY: 5 AN XY: 642374

African (AFR) AF: 0.000112 AC: 3 AN: 26790

American (AMR) AF: 0.00 AC: 0 AN: 28714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23090

East Asian (EAS) AF: 0.00 AC: 0 AN: 28956

South Asian (SAS) AF: 0.00 AC: 0 AN: 73864

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3832

European-Non Finnish (NFE) AF: 0.00000290 AC: 3 AN: 1035904

Other (OTH) AF: 0.0000935 AC: 5 AN: 53470

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152114 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74310

African (AFR) AF: 0.000145 AC: 6 AN: 41448

American (AMR) AF: 0.0000655 AC: 1 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67986

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.63	T
M_CAP	Pathogenic	0.42	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.0
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.089
Sift	Benign	0.15	T
Sift4G	Benign	0.21	T
Polyphen		0.18	B
Vest4		0.30
MutPred		0.46		Gain of loop (P = 0.0312)
MVP		0.061
MPC		0.35
ClinPred		0.48	T
GERP RS		1.6
PromoterAI		0.0072	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.1
Varity_R		0.30
gMVP		0.72
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs1248910043; hg19: chr1-38273552;