Variant chr16-88837678-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000268695.10(GALNS):c.510T>C(p.Tyr170=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0383 in 1,613,984 control chromosomes in the GnomAD database, including 1,423 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 150 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1273 hom. )

Consequence

GALNS
ENST00000268695.10 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.141

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=-0.7).

BP6

Variant 16-88837678-A-G is Benign according to our data. Variant chr16-88837678-A-G is described in ClinVar as [Benign]. Clinvar id is 93180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-88837678-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNS	NM_000512.5 linkuse as main transcript	c.510T>C	p.Tyr170=	synonymous_variant	5/14	ENST00000268695.10	NP_000503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALNS	ENST00000268695.10 linkuse as main transcript	c.510T>C	p.Tyr170=	synonymous_variant	5/14	1	NM_000512.5	ENSP00000268695	P1

Frequencies

GnomAD3 genomes

AF:

0.0388

AC:

5903

AN:

152114

Hom.:

149

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0318

Gnomad AMI

AF:

0.0822

Gnomad AMR

AF:

0.0696

Gnomad ASJ

AF:

0.0374

Gnomad EAS

AF:

0.0313

Gnomad SAS

AF:

0.0840

Gnomad FIN

AF:

0.0192

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0357

Gnomad OTH

AF:

0.0469

GnomAD3 exomes

AF:

0.0457

AC:

11487

AN:

251426

Hom.:

337

AF XY:

0.0473

AC XY:

6432

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.0323

Gnomad AMR exome

AF:

0.0672

Gnomad ASJ exome

AF:

0.0346

Gnomad EAS exome

AF:

0.0352

Gnomad SAS exome

AF:

0.0800

Gnomad FIN exome

AF:

0.0215

Gnomad NFE exome

AF:

0.0391

Gnomad OTH exome

AF:

0.0451

GnomAD4 exome

AF:

0.0383

AC:

55960

AN:

1461752

Hom.:

1273

Cov.:

AF XY:

0.0395

AC XY:

28716

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.0308

Gnomad4 AMR exome

AF:

0.0656

Gnomad4 ASJ exome

AF:

0.0337

Gnomad4 EAS exome

AF:

0.0422

Gnomad4 SAS exome

AF:

0.0786

Gnomad4 FIN exome

AF:

0.0227

Gnomad4 NFE exome

AF:

0.0349

Gnomad4 OTH exome

AF:

0.0382

GnomAD4 genome

AF:

0.0389

AC:

5917

AN:

152232

Hom.:

150

Cov.:

AF XY:

0.0396

AC XY:

2945

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0319

Gnomad4 AMR

AF:

0.0700

Gnomad4 ASJ

AF:

0.0374

Gnomad4 EAS

AF:

0.0306

Gnomad4 SAS

AF:

0.0840

Gnomad4 FIN

AF:

0.0192

Gnomad4 NFE

AF:

0.0357

Gnomad4 OTH

AF:

0.0478

Alfa

AF:

0.0365

Hom.:

Bravo

AF:

0.0410

Asia WGS

AF:

0.0710

AC:

248

AN:

3478

EpiCase

AF:

0.0399

EpiControl

AF:

0.0401

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 12, 2012	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Feb 15, 2019	Variant summary: GALNS c.510T>C alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.046 in 121120 control chromosomes in the ExAC database, including 159 homozygotes. The observed variant frequency is approximately 22-fold of 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. Two ClinVar submission from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as benign. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Mucopolysaccharidosis, MPS-IV-A

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 23, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 25, 2018	This variant is associated with the following publications: (PMID: 24035930, 9452036) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.98

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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