rs76095307

Positions:

• chr16-88835171-C-G

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.898+42G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0558 in 1,554,154 control chromosomes in the GnomAD database, including 2,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (271 hom., cov: 32)
  • Exomes 𝑓: 0.056 (2618 hom.)
• Consequence: GALNS NM_000512.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.35

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 16-88835171-C-G is Benign according to our data. Variant chr16-88835171-C-G is described in ClinVar as [Benign]. Clinvar id is 256339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNS	NM_000512.5	c.898+42G>C		intron_variant		ENST00000268695.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNS	ENST00000268695.10	c.898+42G>C		intron_variant		1	NM_000512.5	P1

Frequencies

GnomAD3 genomes AF: 0.0517 AC: 7861 AN: 152150 Hom.: 270 Cov.: 32

Gnomad AFR AF: 0.0416

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0500

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0807

Gnomad FIN AF: 0.0227

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0606

Gnomad OTH AF: 0.0603

GnomAD3 exomes AF: 0.0543 AC: 8768 AN: 161518 Hom.: 324 AF XY: 0.0576 AC XY: 4902 AN XY: 85140

Gnomad AFR exome AF: 0.0482

Gnomad AMR exome AF: 0.0358

Gnomad ASJ exome AF: 0.123

Gnomad EAS exome AF: 0.000335

Gnomad SAS exome AF: 0.0790

Gnomad FIN exome AF: 0.0224

Gnomad NFE exome AF: 0.0615

Gnomad OTH exome AF: 0.0638

GnomAD4 exome AF: 0.0563 AC: 78932 AN: 1401886 Hom.: 2618 Cov.: 32 AF XY: 0.0578 AC XY: 40013 AN XY: 691764

Gnomad4 AFR exome AF: 0.0442

Gnomad4 AMR exome AF: 0.0416

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.0000828

Gnomad4 SAS exome AF: 0.0819

Gnomad4 FIN exome AF: 0.0231

Gnomad4 NFE exome AF: 0.0567

Gnomad4 OTH exome AF: 0.0571

GnomAD4 genome AF: 0.0516 AC: 7862 AN: 152268 Hom.: 271 Cov.: 32 AF XY: 0.0505 AC XY: 3759 AN XY: 74442

Gnomad4 AFR AF: 0.0416

Gnomad4 AMR AF: 0.0499

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0808

Gnomad4 FIN AF: 0.0227

Gnomad4 NFE AF: 0.0606

Gnomad4 OTH AF: 0.0597

Alfa AF: 0.0622 Hom.: 63

Bravo AF: 0.0522

Asia WGS AF: 0.0310 AC: 108 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs76095307; hg19: chr16-88901579;