16-88813828-T-C

Variant names:

• chr16-88813828-T-C
• rs1135364
• NM_000512.5:c.*611A>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.*611A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 156,244 control chromosomes in the GnomAD database, including 5,753 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5625 hom., cov: 33)
  • Exomes 𝑓: 0.22 (128 hom.)
• Consequence: GALNS NM_000512.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.97
• Publications: 3 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 16-88813828-T-C is Benign according to our data. Variant chr16-88813828-T-C is described in ClinVar as Benign. ClinVar VariationId is 321170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.516 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.*611A>G		3_prime_UTR	Exon 14 of 14	NP_000503.1	P34059
	GALNS	NM_001323544.2		c.*611A>G		3_prime_UTR	Exon 15 of 15	NP_001310473.1
	GALNS	NM_001323543.2		c.*611A>G		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.*611A>G		3_prime_UTR	Exon 14 of 14	ENSP00000268695.5	P34059
	GALNS	ENST00000562593.5	TSL:1	n.5589A>G		non_coding_transcript_exon	Exon 12 of 12
	GALNS	ENST00000862787.1		c.*611A>G		3_prime_UTR	Exon 15 of 15	ENSP00000532846.1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40397 AN: 152024 Hom.: 5620 Cov.: 33

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.292

GnomAD4 exome AF: 0.223 AC: 913 AN: 4102 Hom.: 128 Cov.: 0 AF XY: 0.221 AC XY: 471 AN XY: 2134

African (AFR) AF: 0.292 AC: 7 AN: 24

American (AMR) AF: 0.256 AC: 237 AN: 926

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 4 AN: 16

East Asian (EAS) AF: 0.448 AC: 43 AN: 96

South Asian (SAS) AF: 0.178 AC: 81 AN: 454

European-Finnish (FIN) AF: 0.156 AC: 5 AN: 32

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.206 AC: 496 AN: 2412

Other (OTH) AF: 0.279 AC: 39 AN: 140

GnomAD4 genome AF: 0.266 AC: 40431 AN: 152142 Hom.: 5625 Cov.: 33 AF XY: 0.267 AC XY: 19862 AN XY: 74378

African (AFR) AF: 0.253 AC: 10520 AN: 41506

American (AMR) AF: 0.267 AC: 4084 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 913 AN: 3472

East Asian (EAS) AF: 0.532 AC: 2757 AN: 5180

South Asian (SAS) AF: 0.213 AC: 1025 AN: 4814

European-Finnish (FIN) AF: 0.266 AC: 2815 AN: 10586

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17216 AN: 67982

Other (OTH) AF: 0.291 AC: 615 AN: 2114

Alfa AF: 0.258 Hom.: 2243

Bravo AF: 0.270

Asia WGS AF: 0.329 AC: 1145 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Adenine phosphoribosyltransferase deficiency (1)
-	-	1	Morquio syndrome (1)
-	-	1	Mucopolysaccharidosis, MPS-IV-A (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.98
DANN	Benign	0.20
PhyloP100		-2.0
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: rs1135364; hg19: chr16-88880236;