16-88829729-C-T

Variant names:

• chr16-88829729-C-T
• rs11076720
• NM_000512.5:c.1002+2269G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001323544.2(GALNS):​c.1020+2269G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,262 control chromosomes in the GnomAD database, including 4,384 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4384 hom., cov: 33)
• Consequence: GALNS NM_001323544.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482
• Publications: 13 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323544.2. 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.1002+2269G>A		intron	N/A	NP_000503.1
	GALNS	NM_001323544.2		c.1020+2269G>A		intron	N/A	NP_001310473.1
	GALNS	NM_001323543.2		c.447+2269G>A		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.1002+2269G>A		intron	N/A	ENSP00000268695.5
	GALNS	ENST00000562593.5	TSL:1	n.4411+2269G>A		intron	N/A
	GALNS	ENST00000862787.1		c.1113+2269G>A		intron	N/A	ENSP00000532846.1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33198 AN: 152144 Hom.: 4389 Cov.: 33

Gnomad AFR AF: 0.0828

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.257

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.218 AC: 33200 AN: 152262 Hom.: 4384 Cov.: 33 AF XY: 0.221 AC XY: 16428 AN XY: 74436

African (AFR) AF: 0.0828 AC: 3443 AN: 41580

American (AMR) AF: 0.246 AC: 3757 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 904 AN: 3470

East Asian (EAS) AF: 0.537 AC: 2777 AN: 5168

South Asian (SAS) AF: 0.248 AC: 1196 AN: 4830

European-Finnish (FIN) AF: 0.270 AC: 2864 AN: 10600

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17288 AN: 68012

Other (OTH) AF: 0.256 AC: 541 AN: 2110

Alfa AF: 0.240 Hom.: 3589

Bravo AF: 0.214

Asia WGS AF: 0.327 AC: 1139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.64
PhyloP100		-0.48
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: rs11076720; hg19: chr16-88896137;