Variant rs11076716 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_000512.5(GALNS):c.1483-32G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,549,980 control chromosomes in the GnomAD database, including 43,264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.20 ( 3820 hom., cov: 33)

Exomes 𝑓: 0.23 ( 39444 hom. )

Consequence

GALNS
NM_000512.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.86

Variant links:

Genes affected

GALNS (HGNC:4122): (galactosamine (N-acetyl)-6-sulfatase) This gene encodes N-acetylgalactosamine-6-sulfatase which is a lysosomal exohydrolase required for the degradation of the glycosaminoglycans, keratan sulfate, and chondroitin 6-sulfate. Sequence alterations including point, missense and nonsense mutations, as well as those that affect splicing, result in a deficiency of this enzyme. Deficiencies of this enzyme lead to Morquio A syndrome, a lysosomal storage disorder. [provided by RefSeq, Jul 2008]

GALNS links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 16-88814557-C-G is Benign according to our data. Variant chr16-88814557-C-G is described in ClinVar as [Benign]. Clinvar id is 256332.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNS	NM_000512.5 linkuse as main transcript	c.1483-32G>C		intron_variant		ENST00000268695.10	NP_000503.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
GALNS	ENST00000268695.10 linkuse as main transcript	c.1483-32G>C	intron_variant	1	NM_000512.5	ENSP00000268695	P1
GALNS	ENST00000562593.5 linkuse as main transcript	n.4892-32G>C	intron_variant, non_coding_transcript_variant	1
GALNS	ENST00000567525.5 linkuse as main transcript	c.*954-32G>C	intron_variant, NMD_transcript_variant	2		ENSP00000454484
GALNS	ENST00000568613.5 linkuse as main transcript	c.*1446-32G>C	intron_variant, NMD_transcript_variant	2		ENSP00000457921

Frequencies

GnomAD3 genomes

AF:

0.205

AC:

31150

AN:

152102

Hom.:

3821

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0866

Gnomad AMI

AF:

0.364

Gnomad AMR

AF:

0.236

Gnomad ASJ

AF:

0.246

Gnomad EAS

AF:

0.530

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.252

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.231

Gnomad OTH

AF:

0.251

GnomAD3 exomes

AF:

0.250

AC:

38637

AN:

154460

Hom.:

5564

AF XY:

0.248

AC XY:

20177

AN XY:

81506

show subpopulations

Gnomad AFR exome

AF:

0.0832

Gnomad AMR exome

AF:

0.271

Gnomad ASJ exome

AF:

0.249

Gnomad EAS exome

AF:

0.528

Gnomad SAS exome

AF:

0.206

Gnomad FIN exome

AF:

0.259

Gnomad NFE exome

AF:

0.227

Gnomad OTH exome

AF:

0.259

GnomAD4 exome

AF:

0.231

AC:

322352

AN:

1397760

Hom.:

39444

Cov.:

AF XY:

0.231

AC XY:

158959

AN XY:

689398

show subpopulations

Gnomad4 AFR exome

AF:

0.0842

Gnomad4 AMR exome

AF:

0.272

Gnomad4 ASJ exome

AF:

0.250

Gnomad4 EAS exome

AF:

0.536

Gnomad4 SAS exome

AF:

0.203

Gnomad4 FIN exome

AF:

0.255

Gnomad4 NFE exome

AF:

0.223

Gnomad4 OTH exome

AF:

0.245

GnomAD4 genome

AF:

0.205

AC:

31152

AN:

152220

Hom.:

3820

Cov.:

AF XY:

0.207

AC XY:

15439

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0866

Gnomad4 AMR

AF:

0.236

Gnomad4 ASJ

AF:

0.246

Gnomad4 EAS

AF:

0.530

Gnomad4 SAS

AF:

0.207

Gnomad4 FIN

AF:

0.252

Gnomad4 NFE

AF:

0.231

Gnomad4 OTH

AF:

0.251

Alfa

AF:

0.224

Hom.:

755

Bravo

AF:

0.204

Asia WGS

AF:

0.312

AC:

1085

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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 19, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Mucopolysaccharidosis, MPS-IV-A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.19

DANN

Benign

0.58

BranchPoint Hunter

2.0

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