rs139088253

Positions:

• chr16-88826880-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000512.5(GALNS):​c.1003-42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,552,104 control chromosomes in the GnomAD database, including 323 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0085 (24 hom., cov: 34)
  • Exomes 𝑓: 0.013 (299 hom.)
• Consequence: GALNS NM_000512.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.831

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-88826880-G-A is Benign according to our data. Variant chr16-88826880-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 256331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNS	NM_000512.5	c.1003-42C>T		intron_variant		ENST00000268695.10	NP_000503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALNS	ENST00000268695.10	c.1003-42C>T		intron_variant		1	NM_000512.5	ENSP00000268695.5

Frequencies

GnomAD3 genomes AF: 0.00849 AC: 1292 AN: 152224 Hom.: 23 Cov.: 34

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00772

Gnomad ASJ AF: 0.0328

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0579

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00973

Gnomad OTH AF: 0.00813

GnomAD3 exomes AF: 0.0166 AC: 2584 AN: 155646 Hom.: 77 AF XY: 0.0206 AC XY: 1707 AN XY: 83006

Gnomad AFR exome AF: 0.00248

Gnomad AMR exome AF: 0.00436

Gnomad ASJ exome AF: 0.0272

Gnomad EAS exome AF: 0.0000872

Gnomad SAS exome AF: 0.0652

Gnomad FIN exome AF: 0.00181

Gnomad NFE exome AF: 0.0103

Gnomad OTH exome AF: 0.0186

GnomAD4 exome AF: 0.0129 AC: 18009 AN: 1399762 Hom.: 299 Cov.: 32 AF XY: 0.0146 AC XY: 10072 AN XY: 690930

Gnomad4 AFR exome AF: 0.00171

Gnomad4 AMR exome AF: 0.00404

Gnomad4 ASJ exome AF: 0.0279

Gnomad4 EAS exome AF: 0.0000836

Gnomad4 SAS exome AF: 0.0633

Gnomad4 FIN exome AF: 0.00190

Gnomad4 NFE exome AF: 0.0102

Gnomad4 OTH exome AF: 0.0135

GnomAD4 genome AF: 0.00851 AC: 1297 AN: 152342 Hom.: 24 Cov.: 34 AF XY: 0.00910 AC XY: 678 AN XY: 74486

Gnomad4 AFR AF: 0.00185

Gnomad4 AMR AF: 0.00771

Gnomad4 ASJ AF: 0.0328

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0590

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.00975

Gnomad4 OTH AF: 0.00804

Alfa AF: 0.0115 Hom.: 2

Bravo AF: 0.00706

Asia WGS AF: 0.0180 AC: 61 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Mucopolysaccharidosis, MPS-IV-A Benign:4

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Dec 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 04, 2023	- -
Benign, criteria provided, single submitter	curation	Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	Feb 01, 2021	Allele frequency is >5% in gnomAD v2.1.1 (BA1_stand-alone); allele frequency is greater than expected for disorder (BS1_strong); -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 12, 2019	This variant is associated with the following publications: (PMID: 9375852) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.65

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

Other links and lift over

dbSNP: rs139088253; hg19: chr16-88893288;