chr12-101764985-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024312.5(GNPTAB):c.1932A>G(p.Thr644Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 1,613,608 control chromosomes in the GnomAD database, including 246,506 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T644T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.58 ( 26419 hom., cov: 32)

Exomes 𝑓: 0.54 ( 220087 hom. )

Consequence

GNPTAB
NM_024312.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: -3.79

Publications

33 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: Ambry Genetics, Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
mucolipidosis type III, alpha/beta
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Orphanet, Ambry Genetics

GNPTAB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 12-101764985-T-C is Benign according to our data. Variant chr12-101764985-T-C is described in ClinVar as Benign. ClinVar VariationId is 96119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.79 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024312.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNPTAB	NM_024312.5	MANE Select	c.1932A>G	p.Thr644Thr	synonymous	Exon 13 of 21	NP_077288.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GNPTAB	ENST00000299314.12	TSL:1 MANE Select	c.1932A>G	p.Thr644Thr	synonymous	Exon 13 of 21	ENSP00000299314.7	Q3T906-1
GNPTAB	ENST00000917136.1		c.1953A>G	p.Thr651Thr	synonymous	Exon 13 of 21	ENSP00000587195.1
GNPTAB	ENST00000917134.1		c.1926A>G	p.Thr642Thr	synonymous	Exon 13 of 21	ENSP00000587193.1

Frequencies

GnomAD3 genomes

AF:

0.584

AC:

88676

AN:

151958

Hom.:

26385

Cov.:

show subpopulations

Gnomad AFR

AF:

0.635

Gnomad AMI

AF:

0.644

Gnomad AMR

AF:

0.541

Gnomad ASJ

AF:

0.565

Gnomad EAS

AF:

0.898

Gnomad SAS

AF:

0.644

Gnomad FIN

AF:

0.641

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.525

Gnomad OTH

AF:

0.580

GnomAD2 exomes

AF:

0.590

AC:

148409

AN:

251396

AF XY:

0.590

show subpopulations

Gnomad AFR exome

AF:

0.639

Gnomad AMR exome

AF:

0.575

Gnomad ASJ exome

AF:

0.547

Gnomad EAS exome

AF:

0.905

Gnomad FIN exome

AF:

0.623

Gnomad NFE exome

AF:

0.527

Gnomad OTH exome

AF:

0.571

GnomAD4 exome

AF:

0.544

AC:

794646

AN:

1461532

Hom.:

220087

Cov.:

AF XY:

0.546

AC XY:

396882

AN XY:

727080

show subpopulations

African (AFR)

AF:

0.645

AC:

21598

AN:

33474

American (AMR)

AF:

0.570

AC:

25515

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.558

AC:

14578

AN:

26128

East Asian (EAS)

AF:

0.885

AC:

35147

AN:

39696

South Asian (SAS)

AF:

0.621

AC:

53521

AN:

86248

European-Finnish (FIN)

AF:

0.618

AC:

33016

AN:

53420

Middle Eastern (MID)

AF:

0.603

AC:

3479

AN:

5768

European-Non Finnish (NFE)

AF:

0.516

AC:

573197

AN:

1111696

Other (OTH)

AF:

0.573

AC:

34595

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

20824

41647

62471

83294

104118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16668

33336

50004

66672

83340

<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:

0.584

AC:

88767

AN:

152076

Hom.:

26419

Cov.:

AF XY:

0.589

AC XY:

43818

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.635

AC:

26342

AN:

41478

American (AMR)

AF:

0.542

AC:

8280

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.565

AC:

1960

AN:

3470

East Asian (EAS)

AF:

0.897

AC:

4640

AN:

5174

South Asian (SAS)

AF:

0.643

AC:

3099

AN:

4816

European-Finnish (FIN)

AF:

0.641

AC:

6776

AN:

10566

Middle Eastern (MID)

AF:

0.578

AC:

170

AN:

294

European-Non Finnish (NFE)

AF:

0.525

AC:

35676

AN:

67972

Other (OTH)

AF:

0.585

AC:

1237

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1866

3733

5599

7466

9332

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

744

1488

2232

2976

3720

<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:

0.538

Hom.:

34466

Bravo

AF:

0.580

Asia WGS

AF:

0.777

AC:

2696

AN:

3478

EpiCase

AF:

0.533

EpiControl

AF:

0.535

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

not specified (4)

Mucolipidosis type II (3)

Pseudo-Hurler polydystrophy (2)

Pseudo-Hurler polydystrophy;C2673377:Mucolipidosis type II (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.053

(source)

DANN

Benign

0.42

PhyloP100

-3.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over