13-52028094-T-TA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_021645.6(UTP14C):​c.-486-213dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00778 in 143,996 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0078 (4 hom., cov: 33)
• Consequence: UTP14C NM_021645.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 13-52028094-T-TA is Benign according to our data. Variant chr13-52028094-T-TA is described in ClinVar as Likely_benign. ClinVar VariationId is 1707147.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00778 (1120/143996) while in subpopulation AFR AF = 0.0232 (918/39620). AF 95% confidence interval is 0.0219. There are 4 homozygotes in GnomAd4. There are 538 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTP14C	ENST00000521776.2	TSL:1 MANE Select	c.-486-225_-486-224insA		intron	N/A	ENSP00000428619.1	Q5TAP6
	ALG11	ENST00000521508.2	TSL:1 MANE Select	c.1208-225_1208-224insA		intron	N/A	ENSP00000430236.1	Q2TAA5
	ALG11	ENST00000649340.2		c.1208-228_1208-227insA		intron	N/A	ENSP00000497184.2	A0A3B3IS90

Frequencies

GnomAD3 genomes AF: 0.00773 AC: 1113 AN: 143940 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0230

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00480

Gnomad ASJ AF: 0.000890

Gnomad EAS AF: 0.00219

Gnomad SAS AF: 0.000873

Gnomad FIN AF: 0.00481

Gnomad MID AF: 0.00327

Gnomad NFE AF: 0.000872

Gnomad OTH AF: 0.00825

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

GnomAD4 genome AF: 0.00778 AC: 1120 AN: 143996 Hom.: 4 Cov.: 33 AF XY: 0.00771 AC XY: 538 AN XY: 69778

African (AFR) AF: 0.0232 AC: 918 AN: 39620

American (AMR) AF: 0.00480 AC: 69 AN: 14378

Ashkenazi Jewish (ASJ) AF: 0.000890 AC: 3 AN: 3370

East Asian (EAS) AF: 0.00220 AC: 11 AN: 5010

South Asian (SAS) AF: 0.000876 AC: 4 AN: 4564

European-Finnish (FIN) AF: 0.00481 AC: 41 AN: 8524

Middle Eastern (MID) AF: 0.00357 AC: 1 AN: 280

European-Non Finnish (NFE) AF: 0.000872 AC: 57 AN: 65394

Other (OTH) AF: 0.00819 AC: 16 AN: 1954

Alfa AF: 0.000218 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

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;