GALNS p.Ala241Ala

Variant names:

• chr16-88835759-A-A
• NM_000512.5:c.

Your query was ambiguous. Multiple possible variants found:

• chr16-88835760--
• chr16-88835760-G-A
• chr16-88835760-G-T
• chr16-88835760-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000512.5(GALNS):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GALNS NM_000512.5 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.		exon_region	Exon 7 of 14	NP_000503.1	P34059
	GALNS	NM_001323544.2		c.		exon_region	Exon 8 of 15	NP_001310473.1
	GALNS	NM_001323543.2		c.		exon_region	Exon 6 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.		exon_region	Exon 7 of 14	ENSP00000268695.5	P34059
	GALNS	ENST00000562593.5	TSL:1	n.		exon_region	Exon 5 of 12
	GALNS	ENST00000862787.1		c.		exon_region	Exon 8 of 15	ENSP00000532846.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.23

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-88902167;