Variant rs1064315 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000512.5(GALNS):c.708C>T(p.His236=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,613,812 control chromosomes in the GnomAD database, including 56,159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5278 hom., cov: 33)

Exomes 𝑓: 0.26 ( 50881 hom. )

Consequence

GALNS
NM_000512.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.355

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 16-88835775-G-A is Benign according to our data. Variant chr16-88835775-G-A is described in ClinVar as [Benign]. Clinvar id is 93186.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-88835775-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.355 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.55 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.708C>T	p.His236=	synonymous_variant	7/14	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.708C>T	p.His236=	synonymous_variant	7/14	1	NM_000512.5	ENSP00000268695	P1

Frequencies

GnomAD3 genomes

AF:

0.255

AC:

38808

AN:

152082

Hom.:

5282

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.385

Gnomad AMR

AF:

0.254

Gnomad ASJ

AF:

0.264

Gnomad EAS

AF:

0.568

Gnomad SAS

AF:

0.276

Gnomad FIN

AF:

0.270

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.253

Gnomad OTH

AF:

0.280

GnomAD3 exomes

AF:

0.280

AC:

70392

AN:

251306

Hom.:

10882

AF XY:

0.279

AC XY:

37900

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.209

Gnomad AMR exome

AF:

0.287

Gnomad ASJ exome

AF:

0.264

Gnomad EAS exome

AF:

0.570

Gnomad SAS exome

AF:

0.276

Gnomad FIN exome

AF:

0.270

Gnomad NFE exome

AF:

0.246

Gnomad OTH exome

AF:

0.274

GnomAD4 exome

AF:

0.257

AC:

376140

AN:

1461610

Hom.:

50881

Cov.:

AF XY:

0.258

AC XY:

187948

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.211

Gnomad4 AMR exome

AF:

0.287

Gnomad4 ASJ exome

AF:

0.265

Gnomad4 EAS exome

AF:

0.580

Gnomad4 SAS exome

AF:

0.274

Gnomad4 FIN exome

AF:

0.269

Gnomad4 NFE exome

AF:

0.243

Gnomad4 OTH exome

AF:

0.274

GnomAD4 genome

AF:

0.255

AC:

38820

AN:

152202

Hom.:

5278

Cov.:

AF XY:

0.257

AC XY:

19129

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.209

Gnomad4 AMR

AF:

0.254

Gnomad4 ASJ

AF:

0.264

Gnomad4 EAS

AF:

0.567

Gnomad4 SAS

AF:

0.276

Gnomad4 FIN

AF:

0.270

Gnomad4 NFE

AF:

0.253

Gnomad4 OTH

AF:

0.279

Alfa

AF:

0.254

Hom.:

7546

Bravo

AF:

0.255

Asia WGS

AF:

0.368

AC:

1282

AN:

3478

EpiCase

AF:

0.253

EpiControl

AF:

0.262

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 06, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Oct 30, 2017	Variant summary: The GALNS c.708C>T (p.His236His) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE sites at the locus. However, these predictions have yet to be confirmed by functional studies. This variant was found in 76918/277000 control chromosomes (509 homozygotes) at a frequency of 0.2776823, which is approximately 136 times the estimated maximal expected allele frequency of a pathogenic GALNS variant (0.0020412), strongly suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is 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	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 22, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.052

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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