rs139088253

Variant names:

• chr16-88826880-G-A
• rs139088253
• NM_000512.5:c.1003-42C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-88826880-G-A
• chr16-88826880-G-T

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.1003-42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,552,104 control chromosomes in the GnomAD database, including 323 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0085 (24 hom., cov: 34)
  • Exomes 𝑓: 0.013 (299 hom.)
• Consequence: GALNS NM_000512.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.831
• Publications: 1 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=-0.85).
• BP6: Variant 16-88826880-G-A is Benign according to our data. Variant chr16-88826880-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 256331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0534 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.1003-42C>T		intron	N/A	NP_000503.1	P34059
	GALNS	NM_001323544.2		c.1021-42C>T		intron	N/A	NP_001310473.1
	GALNS	NM_001323543.2		c.448-42C>T		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.1003-42C>T		intron	N/A	ENSP00000268695.5	P34059
	GALNS	ENST00000562593.5	TSL:1	n.4412-42C>T		intron	N/A
	GALNS	ENST00000862787.1		c.1114-42C>T		intron	N/A	ENSP00000532846.1

Frequencies

GnomAD3 genomes AF: 0.00849 AC: 1292 AN: 152224 Hom.: 23 Cov.: 34

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00772

Gnomad ASJ AF: 0.0328

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0579

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00973

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.0166 AC: 2584 AN: 155646 AF XY: 0.0206

Gnomad AFR exome AF: 0.00248

Gnomad AMR exome AF: 0.00436

Gnomad ASJ exome AF: 0.0272

Gnomad EAS exome AF: 0.0000872

Gnomad FIN exome AF: 0.00181

Gnomad NFE exome AF: 0.0103

Gnomad OTH exome AF: 0.0186

GnomAD4 exome AF: 0.0129 AC: 18009 AN: 1399762 Hom.: 299 Cov.: 32 AF XY: 0.0146 AC XY: 10072 AN XY: 690930

African (AFR) AF: 0.00171 AC: 54 AN: 31666

American (AMR) AF: 0.00404 AC: 146 AN: 36140

Ashkenazi Jewish (ASJ) AF: 0.0279 AC: 702 AN: 25192

East Asian (EAS) AF: 0.0000836 AC: 3 AN: 35866

South Asian (SAS) AF: 0.0633 AC: 5033 AN: 79542

European-Finnish (FIN) AF: 0.00190 AC: 92 AN: 48372

Middle Eastern (MID) AF: 0.0294 AC: 133 AN: 4520

European-Non Finnish (NFE) AF: 0.0102 AC: 11065 AN: 1080506

Other (OTH) AF: 0.0135 AC: 781 AN: 57958

GnomAD4 genome AF: 0.00851 AC: 1297 AN: 152342 Hom.: 24 Cov.: 34 AF XY: 0.00910 AC XY: 678 AN XY: 74486

African (AFR) AF: 0.00185 AC: 77 AN: 41582

American (AMR) AF: 0.00771 AC: 118 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.0328 AC: 114 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.0590 AC: 285 AN: 4828

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10624

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00975 AC: 663 AN: 68016

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.0115 Hom.: 2

Bravo AF: 0.00706

Asia WGS AF: 0.0180 AC: 61 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Mucopolysaccharidosis, MPS-IV-A (4)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.65
PhyloP100		0.83
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: rs139088253; hg19: chr16-88893288;