Genetic Variant GNPTAB:c.-41_-39dupGGC (chr12-101830713-A-AGCC) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_024312.5(GNPTAB):c.-41_-39dupGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00056 ( 1 hom., cov: 0)

Exomes 𝑓: 0.00028 ( 1 hom. )

Consequence

GNPTAB
NM_024312.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.123

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

GNPTAB-mucolipidosis
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
mucolipidosis
Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
mucolipidosis type II
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, Genomics England PanelApp
mucolipidosis type III, alpha/beta
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, G2P, Genomics England PanelApp

GNPTAB links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNPTAB	NM_024312.5 link	c.-41_-39dupGGC		5_prime_UTR_variant	Exon 1 of 21	ENST00000299314.12	NP_077288.2
GNPTAB	XM_006719593.4 link	c.-41_-39dupGGC		5_prime_UTR_variant	Exon 1 of 19		XP_006719656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNPTAB	ENST00000299314.12 link	c.-41_-39dupGGC		5_prime_UTR_variant	Exon 1 of 21	1	NM_024312.5	ENSP00000299314.7

Frequencies

GnomAD3 genomes

AF:

0.000502

AC:

AN:

149358

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000199

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000199

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000240

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000401

AC:

AN:

157184

AF XY:

0.000401

show subpopulations

Gnomad AFR exome

AF:

0.00114

Gnomad AMR exome

AF:

0.000420

Gnomad ASJ exome

AF:

0.000123

Gnomad EAS exome

AF:

0.000217

Gnomad FIN exome

AF:

0.0000631

Gnomad NFE exome

AF:

0.000206

Gnomad OTH exome

AF:

0.000470

GnomAD4 exome

AF:

0.000279

AC:

250

AN:

897536

Hom.:

Cov.:

AF XY:

0.000318

AC XY:

148

AN XY:

464970

show subpopulations

African (AFR)

AF:

0.000735

AC:

AN:

17692

American (AMR)

AF:

0.000625

AC:

AN:

35182

Ashkenazi Jewish (ASJ)

AF:

0.0000955

AC:

AN:

20934

East Asian (EAS)

AF:

0.000132

AC:

AN:

30356

South Asian (SAS)

AF:

0.00120

AC:

AN:

69030

European-Finnish (FIN)

AF:

0.0000425

AC:

AN:

47034

Middle Eastern (MID)

AF:

0.00258

AC:

AN:

3096

European-Non Finnish (NFE)

AF:

0.000173

AC:

110

AN:

634306

Other (OTH)

AF:

0.000150

AC:

AN:

39906

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000555

AC:

AN:

149464

Hom.:

Cov.:

AF XY:

0.000632

AC XY:

AN XY:

72800

show subpopulations

African (AFR)

AF:

0.00141

AC:

AN:

41110

American (AMR)

AF:

0.000199

AC:

AN:

15100

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3402

East Asian (EAS)

AF:

0.000199

AC:

AN:

5014

South Asian (SAS)

AF:

0.00104

AC:

AN:

4792

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10112

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000240

AC:

AN:

66666

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000228

Hom.:

2213

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.12

Mutation Taster

=299/1

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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12-101830713-AGCCGCCGCCGCCGCC-AGCCGCCGCCGCCGCCGCC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over