16-88835188-G-C

Variant names:

• chr16-88835188-G-C
• rs113936280
• NM_000512.5:c.898+25C>G

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.898+25C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0559 in 1,561,024 control chromosomes in the GnomAD database, including 2,900 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (271 hom., cov: 32)
  • Exomes 𝑓: 0.056 (2629 hom.)
• Consequence: GALNS NM_000512.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.987
• Publications: 5 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-88835188-G-C is Benign according to our data. Variant chr16-88835188-G-C is described in ClinVar as Benign. ClinVar VariationId is 256338.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0742 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNS	NM_000512.5	MANE Select	c.898+25C>G		intron	N/A	NP_000503.1	P34059
	GALNS	NM_001323544.2		c.916+25C>G		intron	N/A	NP_001310473.1
	GALNS	NM_001323543.2		c.343+25C>G		intron	N/A	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.898+25C>G		intron	N/A	ENSP00000268695.5	P34059
	GALNS	ENST00000562593.5	TSL:1	n.4307+25C>G		intron	N/A
	GALNS	ENST00000862787.1		c.1009+25C>G		intron	N/A	ENSP00000532846.1

Frequencies

GnomAD3 genomes AF: 0.0517 AC: 7862 AN: 152162 Hom.: 270 Cov.: 32

Gnomad AFR AF: 0.0416

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0497

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0807

Gnomad FIN AF: 0.0228

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0606

Gnomad OTH AF: 0.0602

GnomAD2 exomes AF: 0.0538 AC: 9208 AN: 171058 AF XY: 0.0570

Gnomad AFR exome AF: 0.0475

Gnomad AMR exome AF: 0.0354

Gnomad ASJ exome AF: 0.123

Gnomad EAS exome AF: 0.000311

Gnomad FIN exome AF: 0.0228

Gnomad NFE exome AF: 0.0609

Gnomad OTH exome AF: 0.0628

GnomAD4 exome AF: 0.0564 AC: 79395 AN: 1408744 Hom.: 2629 Cov.: 32 AF XY: 0.0579 AC XY: 40275 AN XY: 695810

African (AFR) AF: 0.0440 AC: 1422 AN: 32300

American (AMR) AF: 0.0412 AC: 1510 AN: 36672

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 3168 AN: 25296

East Asian (EAS) AF: 0.0000813 AC: 3 AN: 36882

South Asian (SAS) AF: 0.0818 AC: 6568 AN: 80268

European-Finnish (FIN) AF: 0.0233 AC: 1160 AN: 49718

Middle Eastern (MID) AF: 0.110 AC: 628 AN: 5704

European-Non Finnish (NFE) AF: 0.0569 AC: 61599 AN: 1083488

Other (OTH) AF: 0.0571 AC: 3337 AN: 58416

GnomAD4 genome AF: 0.0516 AC: 7863 AN: 152280 Hom.: 271 Cov.: 32 AF XY: 0.0505 AC XY: 3758 AN XY: 74460

African (AFR) AF: 0.0416 AC: 1727 AN: 41558

American (AMR) AF: 0.0495 AC: 758 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 415 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5176

South Asian (SAS) AF: 0.0808 AC: 389 AN: 4816

European-Finnish (FIN) AF: 0.0228 AC: 242 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0607 AC: 4126 AN: 68022

Other (OTH) AF: 0.0596 AC: 126 AN: 2114

Alfa AF: 0.0359 Hom.: 38

Bravo AF: 0.0521

Asia WGS AF: 0.0310 AC: 108 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Mucopolysaccharidosis, MPS-IV-A (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.056
DANN	Benign	0.46
PhyloP100		-0.99
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs113936280; hg19: chr16-88901596;