13-52028094-TAAAAA-TAAAA

Variant names:

• chr13-52028094-TA-T
• rs142915895
• NM_021645.6:c.-486-213delA

Variant summary

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

The NM_021645.6(UTP14C):​c.-486-213delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 143,942 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0011 (1 hom., cov: 33)
• Consequence: UTP14C NM_021645.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• 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 0 ACMG points.

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.-486-213delA		intron	N/A	NP_067677.4
	ALG11	NM_001004127.3	MANE Select	c.1208-213delA		intron	N/A	NP_001004127.2	Q2TAA5
	ALG11	NR_036571.3		n.66-213delA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTP14C	ENST00000521776.2	TSL:1 MANE Select	c.-486-224delA		intron	N/A	ENSP00000428619.1	Q5TAP6
	ALG11	ENST00000521508.2	TSL:1 MANE Select	c.1208-224delA		intron	N/A	ENSP00000430236.1	Q2TAA5
	ALG11	ENST00000649340.2		c.1208-227delA		intron	N/A	ENSP00000497184.2	A0A3B3IS90

Frequencies

GnomAD3 genomes AF: 0.00108 AC: 155 AN: 143880 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000557

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.000594

Gnomad EAS AF: 0.000597

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00247

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00138

Gnomad OTH AF: 0.000515

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00108 AC: 156 AN: 143942 Hom.: 1 Cov.: 33 AF XY: 0.00109 AC XY: 76 AN XY: 69768

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000581 AC: 23 AN: 39618

American (AMR) AF: 0.00111 AC: 16 AN: 14378

Ashkenazi Jewish (ASJ) AF: 0.000594 AC: 2 AN: 3366

East Asian (EAS) AF: 0.000599 AC: 3 AN: 5010

South Asian (SAS) AF: 0.00 AC: 0 AN: 4568

European-Finnish (FIN) AF: 0.00247 AC: 21 AN: 8512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 276

European-Non Finnish (NFE) AF: 0.00138 AC: 90 AN: 65354

Other (OTH) AF: 0.000511 AC: 1 AN: 1958

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.0
Mutation Taster		=100/0	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: rs142915895; hg19: chr13-52602230;