Genetic Variant GALNS:c.898+25C>G (chr16-88835188-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000512.5(GALNS):c.898+25C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0559 in 1,561,024 control chromosomes in the GnomAD database, including 2,900 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 ( 2629 hom. )

Consequence

GALNS
NM_000512.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.987

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 16-88835188-G-C is Benign according to our data. Variant chr16-88835188-G-C is described in ClinVar as [Benign]. Clinvar id is 256338.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-88835188-G-C is described in Lovd as [Benign].

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 rank	MANE	Protein	UniProt
GALNS	NM_000512.5 link	c.898+25C>G		intron_variant	Intron 8 of 13	ENST00000268695.10	NP_000503.1	P34059Q96I49

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNS	ENST00000268695.10 link	c.898+25C>G		intron_variant	Intron 8 of 13	1	NM_000512.5	ENSP00000268695.5		P34059

Frequencies

GnomAD3 genomes

AF:

0.0517

AC:

7862

AN:

152162

Hom.:

270

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0416

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0497

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0807

Gnomad FIN

AF:

0.0228

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.0606

Gnomad OTH

AF:

0.0602

GnomAD3 exomes

AF:

0.0538

AC:

9208

AN:

171058

Hom.:

339

AF XY:

0.0570

AC XY:

5173

AN XY:

90744

show subpopulations

Gnomad AFR exome

AF:

0.0475

Gnomad AMR exome

AF:

0.0354

Gnomad ASJ exome

AF:

0.123

Gnomad EAS exome

AF:

0.000311

Gnomad SAS exome

AF:

0.0785

Gnomad FIN exome

AF:

0.0228

Gnomad NFE exome

AF:

0.0609

Gnomad OTH exome

AF:

0.0628

GnomAD4 exome

AF:

0.0564

AC:

79395

AN:

1408744

Hom.:

2629

Cov.:

AF XY:

0.0579

AC XY:

40275

AN XY:

695810

show subpopulations

Gnomad4 AFR exome

AF:

0.0440

Gnomad4 AMR exome

AF:

0.0412

Gnomad4 ASJ exome

AF:

0.125

Gnomad4 EAS exome

AF:

0.0000813

Gnomad4 SAS exome

AF:

0.0818

Gnomad4 FIN exome

AF:

0.0233

Gnomad4 NFE exome

AF:

0.0569

Gnomad4 OTH exome

AF:

0.0571

GnomAD4 genome

AF:

0.0516

AC:

7863

AN:

152280

Hom.:

271

Cov.:

AF XY:

0.0505

AC XY:

3758

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0416

Gnomad4 AMR

AF:

0.0495

Gnomad4 ASJ

AF:

0.120

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0808

Gnomad4 FIN

AF:

0.0228

Gnomad4 NFE

AF:

0.0607

Gnomad4 OTH

AF:

0.0596

Alfa

AF:

0.0359

Hom.:

Bravo

AF:

0.0521

Asia WGS

AF:

0.0310

AC:

108

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 24, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 28, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Feb 03, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mucopolysaccharidosis, MPS-IV-A

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.056

DANN

Benign

0.46

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

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