rs35137494

Variant names:

• chr16-88842687-G-A
• rs35137494
• NM_000512.5:c.244+19C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-88842687-G-A
• chr16-88842687-G-C

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.244+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,610,696 control chromosomes in the GnomAD database, including 21,196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1639 hom., cov: 33)
  • Exomes 𝑓: 0.16 (19557 hom.)
• Consequence: GALNS NM_000512.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.462
• Publications: 6 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=-0.93).
• BP6: Variant 16-88842687-G-A is Benign according to our data. Variant chr16-88842687-G-A is described in ClinVar as Benign. ClinVar VariationId is 93174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.174 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.244+19C>T		intron	N/A	NP_000503.1	P34059
	GALNS	NM_001323544.2		c.262+19C>T		intron	N/A	NP_001310473.1
	GALNS	NM_001323543.2		c.-311-716C>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.244+19C>T		intron	N/A	ENSP00000268695.5	P34059
	GALNS	ENST00000562593.5	TSL:1	n.2938C>T		non_coding_transcript_exon	Exon 1 of 12
	GALNS	ENST00000565364.1	TSL:1	n.379+19C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20560 AN: 152138 Hom.: 1642 Cov.: 33

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.0471

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.159

GnomAD2 exomes AF: 0.147 AC: 35918 AN: 244090 AF XY: 0.149

Gnomad AFR exome AF: 0.0597

Gnomad AMR exome AF: 0.167

Gnomad ASJ exome AF: 0.204

Gnomad EAS exome AF: 0.0484

Gnomad FIN exome AF: 0.120

Gnomad NFE exome AF: 0.167

Gnomad OTH exome AF: 0.165

GnomAD4 exome AF: 0.162 AC: 235886 AN: 1458440 Hom.: 19557 Cov.: 33 AF XY: 0.163 AC XY: 118012 AN XY: 725250

African (AFR) AF: 0.0600 AC: 2005 AN: 33436

American (AMR) AF: 0.167 AC: 7420 AN: 44346

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 5351 AN: 26050

East Asian (EAS) AF: 0.0636 AC: 2520 AN: 39640

South Asian (SAS) AF: 0.151 AC: 12930 AN: 85740

European-Finnish (FIN) AF: 0.124 AC: 6497 AN: 52412

Middle Eastern (MID) AF: 0.217 AC: 1248 AN: 5760

European-Non Finnish (NFE) AF: 0.169 AC: 188217 AN: 1110810

Other (OTH) AF: 0.161 AC: 9698 AN: 60246

GnomAD4 genome AF: 0.135 AC: 20563 AN: 152256 Hom.: 1639 Cov.: 33 AF XY: 0.131 AC XY: 9739 AN XY: 74444

African (AFR) AF: 0.0625 AC: 2597 AN: 41560

American (AMR) AF: 0.154 AC: 2350 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 742 AN: 3470

East Asian (EAS) AF: 0.0472 AC: 244 AN: 5172

South Asian (SAS) AF: 0.138 AC: 665 AN: 4830

European-Finnish (FIN) AF: 0.119 AC: 1261 AN: 10616

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11994 AN: 67990

Other (OTH) AF: 0.157 AC: 331 AN: 2110

Alfa AF: 0.150 Hom.: 1092

Bravo AF: 0.136

Asia WGS AF: 0.104 AC: 362 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.073
DANN	Benign	0.54
PhyloP100		-0.46
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: rs35137494; hg19: chr16-88909095; COSMIC: COSV51937210; COSMIC: COSV51937210;