13-52024913-A-T

Variant names:

• chr13-52024913-A-T
• rs727503803
• NM_021645.6:c.-511A>T

Variant summary

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

The NM_021645.6(UTP14C):​c.-511A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UTP14C NM_021645.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.89
• Publications: 0 publications found

Genes affected

UTP14C (HGNC:20321): (UTP14C small subunit processome component) Predicted to be involved in several processes, including meiotic cell cycle; rRNA processing; and spermatogenesis. Located in cytosol and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ALG11 (HGNC:32456): (ALG11 alpha-1,2-mannosyltransferase) This gene encodes a GDP-Man:Man3GlcNAc2-PP-dolichol-alpha1,2-mannosyltransferase which is localized to the cytosolic side of the endoplasmic reticulum (ER) and catalyzes the transfer of the fourth and fifth mannose residue from GDP-mannose (GDP-Man) to Man3GlcNAc2-PP-dolichol and Man4GlcNAc2-PP-dolichol resulting in the production of Man5GlcNAc2-PP-dolichol. Mutations in this gene are associated with congenital disorder of glycosylation type Ip (CDGIP). This gene overlaps but is distinct from the UTP14, U3 small nucleolar ribonucleoprotein, homolog C (yeast) gene. A pseudogene of the GDP-Man:Man3GlcNAc2-PP-dolichol-alpha1,2-mannosyltransferase has been identified on chromosome 19. [provided by RefSeq, Aug 2010]

ALG11 Gene-Disease associations (from GenCC):

• ALG11-congenital disorder of glycosylation

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

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, 0.889

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021645.6. 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
	UTP14C	NM_021645.6	MANE Select	c.-511A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	NP_067677.4
	ALG11	NM_001004127.3	MANE Select	c.1183A>T	p.Met395Leu	missense	Exon 3 of 4	NP_001004127.2	Q2TAA5
	UTP14C	NM_021645.6	MANE Select	c.-511A>T		5_prime_UTR	Exon 1 of 2	NP_067677.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTP14C	ENST00000521776.2	TSL:1 MANE Select	c.-511A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000428619.1	Q5TAP6
	ALG11	ENST00000521508.2	TSL:1 MANE Select	c.1183A>T	p.Met395Leu	missense	Exon 3 of 4	ENSP00000430236.1	Q2TAA5
	UTP14C	ENST00000521776.2	TSL:1 MANE Select	c.-511A>T		5_prime_UTR	Exon 1 of 2	ENSP00000428619.1	Q5TAP6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	26
DANN	Benign	0.97
DEOGEN2	Uncertain	0.67	D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.97
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	0.76	D
MutationAssessor	Pathogenic	3.9	H
PhyloP100		8.9
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.0	D
REVEL	Pathogenic	0.86
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.79
MutPred		0.69		Gain of catalytic residue at M395 (P = 0)
MVP		0.90
MPC		0.30
ClinPred		1.0	D
GERP RS		5.9
PromoterAI		0.017	Neutral
Varity_R		0.97
gMVP		0.87
Mutation Taster		=26/74	disease causing

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: rs727503803; hg19: chr13-52599049;