12-101745969-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_024312.5(GNPTAB):c.*1195A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0778 in 152,198 control chromosomes in the GnomAD database, including 493 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.078 ( 493 hom., cov: 33)

Exomes 𝑓: 0.081 ( 0 hom. )

Consequence

GNPTAB
NM_024312.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.673

Variant links:

Genes affected

GNPTAB (HGNC:29670): (N-acetylglucosamine-1-phosphate transferase subunits alpha and beta) This gene encodes two of three subunit types of the membrane-bound enzyme N-acetylglucosamine-1-phosphotransferase, a heterohexameric complex composed of two alpha, two beta, and two gamma subunits. The encoded protein is proteolytically cleaved at the Lys928-Asp929 bond to yield mature alpha and beta polypeptides while the gamma subunits are the product of a distinct gene (GeneID 84572). In the Golgi apparatus, the heterohexameric complex catalyzes the first step in the synthesis of mannose 6-phosphate recognition markers on certain oligosaccharides of newly synthesized lysosomal enzymes. These recognition markers are essential for appropriate trafficking of lysosomal enzymes. Mutations in this gene have been associated with both mucolipidosis II and mucolipidosis IIIA.[provided by RefSeq, May 2010]

GNPTAB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 12-101745969-T-G is Benign according to our data. Variant chr12-101745969-T-G is described in ClinVar as [Benign]. Clinvar id is 306773.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNPTAB	NM_024312.5 linkuse as main transcript	c.*1195A>C		3_prime_UTR_variant	21/21	ENST00000299314.12
GNPTAB	XM_011538731.3 linkuse as main transcript	c.*1195A>C		3_prime_UTR_variant	21/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNPTAB	ENST00000299314.12 linkuse as main transcript	c.*1195A>C		3_prime_UTR_variant	21/21	1	NM_024312.5	P1	Q3T906-1

Frequencies

GnomAD3 genomes

AF:

0.0779

AC:

11831

AN:

151858

Hom.:

495

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0787

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.0529

Gnomad ASJ

AF:

0.0901

Gnomad EAS

AF:

0.0160

Gnomad SAS

AF:

0.173

Gnomad FIN

AF:

0.0577

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0830

Gnomad OTH

AF:

0.0771

GnomAD4 exome

AF:

0.0811

AC:

AN:

222

Hom.:

Cov.:

AF XY:

0.0843

AC XY:

AN XY:

166

show subpopulations

Gnomad4 AMR exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0833

Gnomad4 OTH exome

AF:

0.0714

GnomAD4 genome

AF:

0.0778

AC:

11822

AN:

151976

Hom.:

493

Cov.:

AF XY:

0.0780

AC XY:

5797

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.0785

Gnomad4 AMR

AF:

0.0528

Gnomad4 ASJ

AF:

0.0901

Gnomad4 EAS

AF:

0.0159

Gnomad4 SAS

AF:

0.174

Gnomad4 FIN

AF:

0.0577

Gnomad4 NFE

AF:

0.0830

Gnomad4 OTH

AF:

0.0763

Alfa

AF:

0.0226

Hom.:

Bravo

AF:

0.0742

Asia WGS

AF:

0.0950

AC:

330

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Pseudo-Hurler polydystrophy

Benign:1

Benign, 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 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. -

Mucolipidosis type II

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

Cadd

Benign

1.9

Dann

Benign

0.71

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