rs78317153

Variant names:

• chr16-88835703-G-A
• rs78317153
• NM_000512.5:c.758+22C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.66
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• mucopolysaccharidosis type 4A

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 256336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0735 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000512.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNS	NM_000512.5	MANE Select	c.758+22C>T		intron	N/A	NP_000503.1
	GALNS	NM_001323544.2		c.776+22C>T		intron	N/A	NP_001310473.1
	GALNS	NM_001323543.2		c.203+22C>T		intron	N/A	NP_001310472.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNS	ENST00000268695.10	TSL:1 MANE Select	c.758+22C>T		intron	N/A	ENSP00000268695.5
	GALNS	ENST00000562593.5	TSL:1	n.4167+22C>T		intron	N/A
	GALNS	ENST00000562931.5	TSL:5	n.346+22C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0501 AC: 7623 AN: 152162 Hom.: 251 Cov.: 33

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

GnomAD2 exomes AF: 0.0519 AC: 13031 AN: 251006 AF XY: 0.0549

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 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.: 32 AF XY: 0.0572 AC XY: 41576 AN XY: 726930

African (AFR) AF: 0.0386 AC: 1292 AN: 33472

American (AMR) AF: 0.0389 AC: 1739 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 3281 AN: 26134

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39694

South Asian (SAS) AF: 0.0810 AC: 6980 AN: 86226

European-Finnish (FIN) AF: 0.0230 AC: 1220 AN: 53016

Middle Eastern (MID) AF: 0.108 AC: 625 AN: 5768

European-Non Finnish (NFE) AF: 0.0563 AC: 62641 AN: 1111842

Other (OTH) AF: 0.0560 AC: 3382 AN: 60380

GnomAD4 genome AF: 0.0501 AC: 7624 AN: 152280 Hom.: 252 Cov.: 33 AF XY: 0.0492 AC XY: 3662 AN XY: 74460

African (AFR) AF: 0.0364 AC: 1515 AN: 41564

American (AMR) AF: 0.0495 AC: 757 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 415 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5172

South Asian (SAS) AF: 0.0800 AC: 386 AN: 4822

European-Finnish (FIN) AF: 0.0227 AC: 241 AN: 10614

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.0604 AC: 4108 AN: 68016

Other (OTH) AF: 0.0578 AC: 122 AN: 2112

Alfa AF: 0.0597 Hom.: 126

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

Submissions by phenotype

not provided Benign:3

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.

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.28
DANN	Benign	0.58
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs78317153; hg19: chr16-88902111; COSMIC: COSV107276889; COSMIC: COSV107276889;