16-88829729-C-T

Position:

• chr16-88829729-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000512.5(GALNS):​c.1002+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_000512.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNS	NM_000512.5	c.1002+2269G>A		intron_variant		ENST00000268695.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNS	ENST00000268695.10	c.1002+2269G>A		intron_variant		1	NM_000512.5	P1
GALNS	ENST00000562593.5	n.4411+2269G>A		intron_variant, non_coding_transcript_variant		1
GALNS	ENST00000567525.5	c.*473+2269G>A		intron_variant, NMD_transcript_variant		2
GALNS	ENST00000568613.5	c.*965+2269G>A		intron_variant, NMD_transcript_variant		2

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

Gnomad4 AFR AF: 0.0828

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.256

Alfa AF: 0.241 Hom.: 3035

Bravo AF: 0.214

Asia WGS AF: 0.327 AC: 1139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.64

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

Other links and lift over

dbSNP: rs11076720; hg19: chr16-88896137;