chr16-88835869-G-A

Variant names:

Variant summary

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

The NM_000512.5(GALNS):c.634-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0935 in 1,613,416 control chromosomes in the GnomAD database, including 7,807 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.091 ( 695 hom., cov: 33)

Exomes 𝑓: 0.094 ( 7112 hom. )

Consequence

GALNS
NM_000512.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.72

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

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 16-88835869-G-A is Benign according to our data. Variant chr16-88835869-G-A is described in ClinVar as [Benign]. Clinvar id is 93182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-88835869-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNS	NM_000512.5 link	c.634-20C>T		intron_variant	Intron 6 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.634-20C>T		intron_variant	Intron 6 of 13	1	NM_000512.5	ENSP00000268695.5		P34059

Frequencies

GnomAD3 genomes

AF:

0.0905

AC:

13769

AN:

152178

Hom.:

692

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0732

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.156

Gnomad EAS

AF:

0.0317

Gnomad SAS

AF:

0.161

Gnomad FIN

AF:

0.0418

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.0965

Gnomad OTH

AF:

0.107

GnomAD3 exomes

AF:

0.0981

AC:

24607

AN:

250874

Hom.:

1414

AF XY:

0.103

AC XY:

13911

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.0758

Gnomad AMR exome

AF:

0.103

Gnomad ASJ exome

AF:

0.158

Gnomad EAS exome

AF:

0.0351

Gnomad SAS exome

AF:

0.152

Gnomad FIN exome

AF:

0.0445

Gnomad NFE exome

AF:

0.0997

Gnomad OTH exome

AF:

0.106

GnomAD4 exome

AF:

0.0938

AC:

137095

AN:

1461120

Hom.:

7112

Cov.:

AF XY:

0.0966

AC XY:

70207

AN XY:

726854

show subpopulations

Gnomad4 AFR exome

AF:

0.0744

Gnomad4 AMR exome

AF:

0.106

Gnomad4 ASJ exome

AF:

0.159

Gnomad4 EAS exome

AF:

0.0418

Gnomad4 SAS exome

AF:

0.156

Gnomad4 FIN exome

AF:

0.0457

Gnomad4 NFE exome

AF:

0.0914

Gnomad4 OTH exome

AF:

0.0941

GnomAD4 genome

AF:

0.0905

AC:

13787

AN:

152296

Hom.:

695

Cov.:

AF XY:

0.0901

AC XY:

6708

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0733

Gnomad4 AMR

AF:

0.121

Gnomad4 ASJ

AF:

0.156

Gnomad4 EAS

AF:

0.0314

Gnomad4 SAS

AF:

0.161

Gnomad4 FIN

AF:

0.0418

Gnomad4 NFE

AF:

0.0965

Gnomad4 OTH

AF:

0.108

Alfa

AF:

0.0968

Hom.:

203

Bravo

AF:

0.0934

Asia WGS

AF:

0.0980

AC:

338

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Jan 26, 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

- -

Jun 16, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Feb 15, 2019

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: GALNS c.634-20C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. The variant allele was found at a frequency of 0.096 in 276718 control chromosomes in the gnomAD database, including 1472 homozygotes. The observed variant frequency is approximately 47-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in GALNS causing Mucopolysaccharidosis Type IVA (Morquio Syndrome A) phenotype (0.002), strongly suggesting that the variant is benign. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as benign. Based on the evidence outlined above, the variant was classified as benign. -

Mucopolysaccharidosis, MPS-IV-A

Benign:4

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 07, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 23, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.40

DANN

Benign

0.45

BranchPoint Hunter

1.0

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