Variant 13-52024999-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_021645.6(UTP14C):c.-487+62A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,501,530 control chromosomes in the GnomAD database, including 10,658 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 817 hom., cov: 32)

Exomes 𝑓: 0.12 ( 9841 hom. )

Consequence

UTP14C
NM_021645.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.321

Variant links:

Genes affected

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:

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:

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 (BayesDel_noAF=-0.84).

BP6

Variant 13-52024999-A-G is Benign according to our data. Variant chr13-52024999-A-G is described in ClinVar as [Benign]. Clinvar id is 1242428.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	Effect	MANE
ALG11	NM_001004127.3 linkuse as main transcript	c.1207+62A>G	intron_variant	ENST00000521508.2
UTP14C	NM_021645.6 linkuse as main transcript	c.-487+62A>G	intron_variant	ENST00000521776.2
ALG11	NR_036571.3 linkuse as main transcript	n.66-3320A>G	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG11	ENST00000521508.2 linkuse as main transcript	c.1207+62A>G		intron_variant		1	NM_001004127.3	P4
UTP14C	ENST00000521776.2 linkuse as main transcript	c.-487+62A>G		intron_variant		1	NM_021645.6	P1

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15714

AN:

152094

Hom.:

817

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0614

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.0619

Gnomad SAS

AF:

0.0853

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.115

GnomAD4 exome

AF:

0.118

AC:

158738

AN:

1349320

Hom.:

9841

AF XY:

0.117

AC XY:

79137

AN XY:

677120

show subpopulations

Gnomad4 AFR exome

AF:

0.0609

Gnomad4 AMR exome

AF:

0.116

Gnomad4 ASJ exome

AF:

0.122

Gnomad4 EAS exome

AF:

0.0515

Gnomad4 SAS exome

AF:

0.0894

Gnomad4 FIN exome

AF:

0.120

Gnomad4 NFE exome

AF:

0.124

Gnomad4 OTH exome

AF:

0.115

GnomAD4 genome

AF:

0.103

AC:

15723

AN:

152210

Hom.:

817

Cov.:

AF XY:

0.103

AC XY:

7656

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0615

Gnomad4 AMR

AF:

0.123

Gnomad4 ASJ

AF:

0.124

Gnomad4 EAS

AF:

0.0621

Gnomad4 SAS

AF:

0.0850

Gnomad4 FIN

AF:

0.123

Gnomad4 NFE

AF:

0.123

Gnomad4 OTH

AF:

0.114

Alfa

AF:

0.113

Hom.:

192

Bravo

AF:

0.103

Asia WGS

AF:

0.0680

AC:

237

AN:

3478

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	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 31, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 20% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 19. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.5

DANN

Benign

0.74

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