rs78317153

Positions:

• chr16-88835703-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.758+22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.055 in 1,613,532 control chromosomes in the GnomAD database, including 2,915 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (252 hom., cov: 33)
  • Exomes 𝑓: 0.056 (2663 hom.)
• Consequence: GALNS NM_000512.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.66

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=-0.9).
• BP6: Variant 16-88835703-G-A is Benign according to our data. Variant chr16-88835703-G-A is described in ClinVar as [Benign]. Clinvar id is 256336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-88835703-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNS	NM_000512.5	c.758+22C>T		intron_variant		ENST00000268695.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNS	ENST00000268695.10	c.758+22C>T		intron_variant		1	NM_000512.5	P1

Frequencies

GnomAD3 genomes AF: 0.0501 AC: 7623 AN: 152162 Hom.: 251 Cov.: 33

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.0496

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0800

Gnomad FIN AF: 0.0227

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0604

Gnomad OTH AF: 0.0584

GnomAD3 exomes AF: 0.0519 AC: 13031 AN: 251006 Hom.: 461 AF XY: 0.0549 AC XY: 7445 AN XY: 135718

Gnomad AFR exome AF: 0.0377

Gnomad AMR exome AF: 0.0340

Gnomad ASJ exome AF: 0.123

Gnomad EAS exome AF: 0.000489

Gnomad SAS exome AF: 0.0765

Gnomad FIN exome AF: 0.0227

Gnomad NFE exome AF: 0.0598

Gnomad OTH exome AF: 0.0604

GnomAD4 exome AF: 0.0555 AC: 81165 AN: 1461252 Hom.: 2663 Cov.: 32 AF XY: 0.0572 AC XY: 41576 AN XY: 726930

Gnomad4 AFR exome AF: 0.0386

Gnomad4 AMR exome AF: 0.0389

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0810

Gnomad4 FIN exome AF: 0.0230

Gnomad4 NFE exome AF: 0.0563

Gnomad4 OTH exome AF: 0.0560

GnomAD4 genome AF: 0.0501 AC: 7624 AN: 152280 Hom.: 252 Cov.: 33 AF XY: 0.0492 AC XY: 3662 AN XY: 74460

Gnomad4 AFR AF: 0.0364

Gnomad4 AMR AF: 0.0495

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0800

Gnomad4 FIN AF: 0.0227

Gnomad4 NFE AF: 0.0604

Gnomad4 OTH AF: 0.0578

Alfa AF: 0.0618 Hom.: 82

Bravo AF: 0.0504

Asia WGS AF: 0.0310 AC: 107 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 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, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Apr 24, 2017	- -

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	-0.90
CADD	Benign	0.28
DANN	Benign	0.58

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: rs78317153; hg19: chr16-88902111;