13-52029312-A-G

Position:

chr13-52029312-A-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_021645.6(UTP14C):c.508A>G(p.Ile170Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00596 in 1,614,194 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0062 ( 34 hom. )

Consequence

UTP14C
NM_021645.6 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: -0.171

Variant links:

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]

UTP14C links:

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 links:

ALG11 (HGNC:):

ALG11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007573843).

BP6

Variant 13-52029312-A-G is Benign according to our data. Variant chr13-52029312-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 235513.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAdExome4 at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UTP14C	NM_021645.6 linkuse as main transcript	c.508A>G	p.Ile170Val	missense_variant	2/2	ENST00000521776.2	NP_067677.4	Q5TAP6A0A024RDV0
ALG11	NM_001004127.3 linkuse as main transcript	c.*722A>G		3_prime_UTR_variant	4/4	ENST00000521508.2	NP_001004127.2	Q2TAA5
ALG11	NR_036571.3 linkuse as main transcript	n.1059A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UTP14C	ENST00000521776.2 linkuse as main transcript	c.508A>G	p.Ile170Val	missense_variant	2/2	1	NM_021645.6	ENSP00000428619.1		Q5TAP6
ALG11	ENST00000521508.2 linkuse as main transcript	c.*722A>G		3_prime_UTR_variant	4/4	1	NM_001004127.3	ENSP00000430236.1		Q2TAA5

Frequencies

GnomAD3 genomes

AF:

0.00410

AC:

624

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00248

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00745

Gnomad OTH

AF:

0.00623

GnomAD3 exomes

AF:

0.00354

AC:

891

AN:

251402

Hom.:

AF XY:

0.00380

AC XY:

516

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00281

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000555

Gnomad FIN exome

AF:

0.000647

Gnomad NFE exome

AF:

0.00626

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00616

AC:

9000

AN:

1461892

Hom.:

Cov.:

106

AF XY:

0.00604

AC XY:

4392

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00125

Gnomad4 AMR exome

AF:

0.00295

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000556

Gnomad4 FIN exome

AF:

0.000861

Gnomad4 NFE exome

AF:

0.00751

Gnomad4 OTH exome

AF:

0.00626

GnomAD4 genome

AF:

0.00410

AC:

624

AN:

152302

Hom.:

Cov.:

AF XY:

0.00373

AC XY:

278

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00745

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00569

Hom.:

Bravo

AF:

0.00391

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00674

AC:

ExAC

AF:

0.00347

AC:

421

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00725

EpiControl

AF:

0.00593

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	UTP14C: BP4, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 09, 2016	- -

ALG11-congenital disorder of glycosylation

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.9

DANN

Benign

0.94

DEOGEN2

Benign

0.0011

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.76

M_CAP

Benign

0.0023

MetaRNN

Benign

0.0076

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.17

REVEL

Benign

0.027

Sift

Benign

0.20

Sift4G

Benign

0.89

Polyphen

0.24

Vest4

0.042

MVP

0.23

MPC

0.099

ClinPred

0.0016

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.031

gMVP

0.071

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over