16-88814232-C-A

Variant names:

• chr16-88814232-C-A
• rs886052452
• NM_000512.5:c.*207G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000512.5(GALNS):​c.*207G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 525,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: GALNS NM_000512.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0530
• Publications: 0 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: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNS	NM_000512.5	MANE Select	c.*207G>T		3_prime_UTR	Exon 14 of 14	NP_000503.1	P34059
	GALNS	NM_001323544.2		c.*207G>T		3_prime_UTR	Exon 15 of 15	NP_001310473.1
	GALNS	NM_001323543.2		c.*207G>T		3_prime_UTR	Exon 13 of 13	NP_001310472.1	Q6YL38

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNS	ENST00000268695.10	TSL:1 MANE Select	c.*207G>T		3_prime_UTR	Exon 14 of 14	ENSP00000268695.5	P34059
	GALNS	ENST00000562593.5	TSL:1	n.5185G>T		non_coding_transcript_exon	Exon 12 of 12
	GALNS	ENST00000862787.1		c.*207G>T		3_prime_UTR	Exon 15 of 15	ENSP00000532846.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.0000133 AC: 7 AN: 525102 Hom.: 0 Cov.: 6 AF XY: 0.0000144 AC XY: 4 AN XY: 276994

African (AFR) AF: 0.00 AC: 0 AN: 14524

American (AMR) AF: 0.00 AC: 0 AN: 25766

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15780

East Asian (EAS) AF: 0.00 AC: 0 AN: 31166

South Asian (SAS) AF: 0.00 AC: 0 AN: 51846

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30834

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2210

European-Non Finnish (NFE) AF: 0.0000216 AC: 7 AN: 324278

Other (OTH) AF: 0.00 AC: 0 AN: 28698

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Morquio syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.40
PhyloP100		0.053

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: rs886052452; hg19: chr16-88880640;