rs35137494

chr16-88842687-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.244+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,610,696 control chromosomes in the GnomAD database, including 21,196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1639 hom., cov: 33)
  • Exomes 𝑓: 0.16 (19557 hom.)
• Consequence: GALNS NM_000512.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.462

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 16-88842687-G-A is Benign according to our data. Variant chr16-88842687-G-A is described in ClinVar as [Benign]. Clinvar id is 93174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-88842687-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNS	NM_000512.5	c.244+19C>T		intron_variant		ENST00000268695.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNS	ENST00000268695.10	c.244+19C>T		intron_variant		1	NM_000512.5	P1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20560 AN: 152138 Hom.: 1642 Cov.: 33

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.0471

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.159

GnomAD3 exomes AF: 0.147 AC: 35918 AN: 244090 Hom.: 2855 AF XY: 0.149 AC XY: 19760 AN XY: 132514

Gnomad AFR exome AF: 0.0597

Gnomad AMR exome AF: 0.167

Gnomad ASJ exome AF: 0.204

Gnomad EAS exome AF: 0.0484

Gnomad SAS exome AF: 0.152

Gnomad FIN exome AF: 0.120

Gnomad NFE exome AF: 0.167

Gnomad OTH exome AF: 0.165

GnomAD4 exome AF: 0.162 AC: 235886 AN: 1458440 Hom.: 19557 Cov.: 33 AF XY: 0.163 AC XY: 118012 AN XY: 725250

Gnomad4 AFR exome AF: 0.0600

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.205

Gnomad4 EAS exome AF: 0.0636

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.169

Gnomad4 OTH exome AF: 0.161

GnomAD4 genome AF: 0.135 AC: 20563 AN: 152256 Hom.: 1639 Cov.: 33 AF XY: 0.131 AC XY: 9739 AN XY: 74444

Gnomad4 AFR AF: 0.0625

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.0472

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.157

Alfa AF: 0.162 Hom.: 599

Bravo AF: 0.136

Asia WGS AF: 0.104 AC: 362 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 06, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Nov 15, 2019	- -

Mucopolysaccharidosis, MPS-IV-A Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -

not provided Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Dec 15, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.073
Dann	Benign	0.54

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: rs35137494; hg19: chr16-88909095; COSMIC: COSV51937210; COSMIC: COSV51937210;