1-37807823-C-T

Variant names:

• chr1-37807823-C-T
• rs772402590
• NM_198446.3:c.-582C>T

Variant summary

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

The NM_198446.3(C1orf122):​c.-582C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: C1orf122 NM_198446.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• Publications: 0 publications found

Genes affected

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

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 Gene-Disease associations (from GenCC):

• Galloway-Mowat syndrome 10

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

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=0.091786325).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198446.3. 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
	C1orf122	NM_198446.3	MANE Select	c.-582C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_940848.2	Q6ZSJ8-1
	YRDC	NM_024640.4	MANE Select	c.358G>A	p.Val120Ile	missense	Exon 1 of 5	NP_078916.3
	C1orf122	NM_198446.3	MANE Select	c.-582C>T		5_prime_UTR	Exon 1 of 3	NP_940848.2	Q6ZSJ8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf122	ENST00000373042.5	TSL:1 MANE Select	c.-582C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000362133.4	Q6ZSJ8-1
	C1orf122	ENST00000373043.1	TSL:1	c.-862C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000362134.1	Q6ZSJ8-2
	YRDC	ENST00000373044.3	TSL:1 MANE Select	c.358G>A	p.Val120Ile	missense	Exon 1 of 5	ENSP00000362135.2	Q86U90

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152180 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1357588 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 669666

African (AFR) AF: 0.00 AC: 0 AN: 29242

American (AMR) AF: 0.00 AC: 0 AN: 33684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24436

East Asian (EAS) AF: 0.00 AC: 0 AN: 32890

South Asian (SAS) AF: 0.00 AC: 0 AN: 78152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3990

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1065824

Other (OTH) AF: 0.00 AC: 0 AN: 56252

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152180 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74348

African (AFR) AF: 0.0000241 AC: 1 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.095	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.094
FATHMM_MKL	Benign	0.35	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.37	N
PhyloP100		1.4
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	0.55	N
REVEL	Benign	0.048
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.16	B
Vest4		0.13
MutPred		0.56		Loss of MoRF binding (P = 0.0997)
MVP		0.17
MPC		0.23
ClinPred		0.41	T
GERP RS		4.9
PromoterAI		-0.045	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.056
gMVP		0.30
Mutation Taster		=291/9	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: rs772402590; hg19: chr1-38273495;