rs3742290

Positions:

chr13-52029105-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021645.6(UTP14C):c.301A>G(p.Thr101Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,614,132 control chromosomes in the GnomAD database, including 11,325 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 811 hom., cov: 32)

Exomes 𝑓: 0.12 ( 10514 hom. )

Consequence

UTP14C
NM_021645.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.590

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001627624).

BP6

Variant 13-52029105-A-G is Benign according to our data. Variant chr13-52029105-A-G is described in ClinVar as [Benign]. Clinvar id is 312423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
UTP14C	NM_021645.6 linkuse as main transcript	c.301A>G	p.Thr101Ala	missense_variant	2/2	ENST00000521776.2	NP_067677.4
ALG11	NM_001004127.3 linkuse as main transcript	c.*515A>G		3_prime_UTR_variant	4/4	ENST00000521508.2	NP_001004127.2
ALG11	NR_036571.3 linkuse as main transcript	n.852A>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.301A>G	p.Thr101Ala	missense_variant	2/2	1	NM_021645.6	ENSP00000428619	P1
ALG11	ENST00000521508.2 linkuse as main transcript	c.*515A>G		3_prime_UTR_variant	4/4	1	NM_001004127.3	ENSP00000430236	P4

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15709

AN:

152136

Hom.:

811

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0613

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.0621

Gnomad SAS

AF:

0.0855

Gnomad FIN

AF:

0.122

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.116

GnomAD3 exomes

AF:

0.111

AC:

27943

AN:

251436

Hom.:

1695

AF XY:

0.112

AC XY:

15266

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.0615

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.117

Gnomad EAS exome

AF:

0.0693

Gnomad SAS exome

AF:

0.0876

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.128

Gnomad OTH exome

AF:

0.129

GnomAD4 exome

AF:

0.117

AC:

170743

AN:

1461878

Hom.:

10514

Cov.:

106

AF XY:

0.116

AC XY:

84512

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0600

Gnomad4 AMR exome

AF:

0.116

Gnomad4 ASJ exome

AF:

0.121

Gnomad4 EAS exome

AF:

0.0518

Gnomad4 SAS exome

AF:

0.0890

Gnomad4 FIN exome

AF:

0.118

Gnomad4 NFE exome

AF:

0.123

Gnomad4 OTH exome

AF:

0.114

GnomAD4 genome

AF:

0.103

AC:

15719

AN:

152254

Hom.:

811

Cov.:

AF XY:

0.103

AC XY:

7653

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0613

Gnomad4 AMR

AF:

0.123

Gnomad4 ASJ

AF:

0.124

Gnomad4 EAS

AF:

0.0622

Gnomad4 SAS

AF:

0.0853

Gnomad4 FIN

AF:

0.122

Gnomad4 NFE

AF:

0.123

Gnomad4 OTH

AF:

0.114

Alfa

AF:

0.118

Hom.:

2451

Bravo

AF:

0.104

TwinsUK

AF:

0.127

AC:

471

ALSPAC

AF:

0.117

AC:

451

ESP6500AA

AF:

0.0631

AC:

278

ESP6500EA

AF:

0.119

AC:

1023

ExAC

AF:

0.112

AC:

13594

Asia WGS

AF:

0.0680

AC:

237

AN:

3478

EpiCase

AF:

0.128

EpiControl

AF:

0.131

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

ALG11-congenital disorder of glycosylation

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.35

DANN

Benign

0.82

DEOGEN2

Benign

0.0024

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.71

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.020

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.50

REVEL

Benign

0.011

Sift

Benign

0.79

Sift4G

Benign

0.83

Polyphen

0.0040

Vest4

0.024

MPC

0.078

ClinPred

0.0032

GERP RS

0.15

Varity_R

0.028

gMVP

0.050

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