dbSNP rs10492086: GNPTAB:c.203+2514T>C (chr12-101794163-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024312.5(GNPTAB):c.203+2514T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,122 control chromosomes in the GnomAD database, including 2,942 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 2942 hom., cov: 32)

Consequence

GNPTAB
NM_024312.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.635

Publications

6 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
GNPTAB	NM_024312.5 link	c.203+2514T>C	intron_variant	Intron 2 of 20	ENST00000299314.12	NP_077288.2
GNPTAB	XM_011538731.3 link	c.122+2514T>C	intron_variant	Intron 2 of 20		XP_011537033.1
GNPTAB	XM_006719593.4 link	c.203+2514T>C	intron_variant	Intron 2 of 18		XP_006719656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNPTAB	ENST00000299314.12 link	c.203+2514T>C		intron_variant	Intron 2 of 20	1	NM_024312.5	ENSP00000299314.7
GNPTAB	ENST00000549940.5 link	c.203+2514T>C		intron_variant	Intron 2 of 10	1		ENSP00000449150.1

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29506

AN:

152004

Hom.:

2941

Cov.:

show subpopulations

Gnomad AFR

AF:

0.241

Gnomad AMI

AF:

0.318

Gnomad AMR

AF:

0.145

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.140

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.200

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.173

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.194

AC:

29528

AN:

152122

Hom.:

2942

Cov.:

AF XY:

0.195

AC XY:

14470

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.240

AC:

9976

AN:

41498

American (AMR)

AF:

0.145

AC:

2208

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

398

AN:

3472

East Asian (EAS)

AF:

0.140

AC:

724

AN:

5180

South Asian (SAS)

AF:

0.222

AC:

1068

AN:

4820

European-Finnish (FIN)

AF:

0.200

AC:

2115

AN:

10576

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.181

AC:

12330

AN:

67988

Other (OTH)

AF:

0.179

AC:

378

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1245

2491

3736

4982

6227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

318

636

954

1272

1590

<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:

0.186

Hom.:

1382

Bravo

AF:

0.190

Asia WGS

AF:

0.197

AC:

684

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.5

(source)

DANN

Benign

0.73

PhyloP100

0.64

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over