dbSNP rs139088253: GALNS:c.1003-42C>T (chr16-88826880-G-A) – 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.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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.831

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=-0.85).

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 rank	MANE	Protein	UniProt
GALNS	NM_000512.5 link	c.1003-42C>T		intron_variant	Intron 9 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.1003-42C>T		intron_variant	Intron 9 of 13	1	NM_000512.5	ENSP00000268695.5		P34059

Frequencies

GnomAD3 genomes

AF:

0.00849

AC:

1292

AN:

152224

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.0206

AC XY:

1707

AN XY:

83006

show subpopulations

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.:

AF XY:

0.0146

AC XY:

10072

AN XY:

690930

show subpopulations

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.:

Cov.:

AF XY:

0.00910

AC XY:

678

AN XY:

74486

show subpopulations

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.:

Bravo

AF:

0.00706

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Mucopolysaccharidosis, MPS-IV-A

Benign:4

Feb 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 04, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 01, 2021

Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

Allele frequency is >5% in gnomAD v2.1.1 (BA1_stand-alone); allele frequency is greater than expected for disorder (BS1_strong); -

Nov 07, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Jun 12, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 9375852) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely 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

-0.85

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

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