NM_021645.6:c.-486-217_-486-213delAAAAA

Variant names:

• chr13-52028094-TAAAAA-T
• rs142915895
• NM_021645.6:c.-486-217_-486-213delAAAAA

Variant summary

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

The NM_021645.6(UTP14C):​c.-486-217_-486-213delAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000693 in 144,240 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000069 (0 hom., cov: 33)
• Consequence: UTP14C NM_021645.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.-486-217_-486-213delAAAAA		intron	N/A	NP_067677.4
	ALG11	NM_001004127.3	MANE Select	c.1208-217_1208-213delAAAAA		intron	N/A	NP_001004127.2	Q2TAA5
	ALG11	NR_036571.3		n.66-217_66-213delAAAAA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTP14C	ENST00000521776.2	TSL:1 MANE Select	c.-486-224_-486-220delAAAAA		intron	N/A	ENSP00000428619.1	Q5TAP6
	ALG11	ENST00000521508.2	TSL:1 MANE Select	c.1208-224_1208-220delAAAAA		intron	N/A	ENSP00000430236.1	Q2TAA5
	ALG11	ENST00000649340.2		c.1208-227_1208-223delAAAAA		intron	N/A	ENSP00000497184.2	A0A3B3IS90

Frequencies

GnomAD3 genomes AF: 0.00000693 AC: 1 AN: 144240 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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000153

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000693 AC: 1 AN: 144240 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 69896

African (AFR) AF: 0.00 AC: 0 AN: 39558

American (AMR) AF: 0.00 AC: 0 AN: 14396

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3372

East Asian (EAS) AF: 0.00 AC: 0 AN: 5024

South Asian (SAS) AF: 0.00 AC: 0 AN: 4588

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.0000153 AC: 1 AN: 65530

Other (OTH) AF: 0.00 AC: 0 AN: 1946

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
PhyloP100		1.9

Splicing

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

Other links and lift over

dbSNP: rs142915895; hg19: chr13-52602230;