dbSNP rs78317153: GALNS:c.758+22C>T (chr16-88835703-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.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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.66

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=-0.9).

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 rank	MANE	Protein	UniProt
GALNS	NM_000512.5 link	c.758+22C>T		intron_variant	Intron 7 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.758+22C>T		intron_variant	Intron 7 of 13	1	NM_000512.5	ENSP00000268695.5		P34059

Frequencies

GnomAD3 genomes

AF:

0.0501

AC:

7623

AN:

152162

Hom.:

251

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0572

AC XY:

41576

AN XY:

726930

show subpopulations

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.:

AF XY:

0.0492

AC XY:

3662

AN XY:

74460

show subpopulations

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.:

Bravo

AF:

0.0504

Asia WGS

AF:

0.0310

AC:

107

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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 18, 2018

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. -

not specified

Benign:1

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

-0.90

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

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