Genetic Variant GALNS:c.898+42G>C (chr16-88835171-C-G) – 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+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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.35

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=-0.93).

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 rank	MANE	Protein	UniProt
GALNS	NM_000512.5 link	c.898+42G>C		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+42G>C		intron_variant	Intron 8 of 13	1	NM_000512.5	ENSP00000268695.5		P34059

Frequencies

GnomAD3 genomes

AF:

0.0517

AC:

7861

AN:

152150

Hom.:

270

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0578

AC XY:

40013

AN XY:

691764

show subpopulations

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.:

AF XY:

0.0505

AC XY:

3759

AN XY:

74442

show subpopulations

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.:

Bravo

AF:

0.0522

Asia WGS

AF:

0.0310

AC:

108

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 28, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

-0.93

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

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