rs1064315

Variant names:

• chr16-88835775-G-A
• rs1064315
• NM_000512.5:c.708C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-88835775-G-A
• chr16-88835775-G-C
• chr16-88835775-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000512.5(GALNS):​c.708C>T​(p.His236His) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.355

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]

ACMG classification

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 rank	MANE	Protein	UniProt
GALNS	NM_000512.5	c.708C>T	p.His236His	synonymous_variant	Exon 7 of 14	ENST00000268695.10	NP_000503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNS	ENST00000268695.10	c.708C>T	p.His236His	synonymous_variant	Exon 7 of 14	1	NM_000512.5	ENSP00000268695.5

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38808 AN: 152082 Hom.: 5282 Cov.: 33

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

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.: 44 AF XY: 0.258 AC XY: 187948 AN XY: 727100

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.: 33 AF XY: 0.257 AC XY: 19129 AN XY: 74404

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

Submissions by phenotype

not specified Benign:3

Nov 06, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 30, 2017

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mucopolysaccharidosis, MPS-IV-A Benign:3

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 22, 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	-0.60
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

Other links and lift over

dbSNP: rs1064315; hg19: chr16-88902183; COSMIC: COSV51935790; COSMIC: COSV51935790;