chr16-88813738-G-C

Position:

• chr16-88813738-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000512.5(GALNS):​c.*701C>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 0.222 in 152,528 control chromosomes in the GnomAD database, including 4,424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4418 hom., cov: 33)
  • Exomes 𝑓: 0.15 (6 hom.)
• Consequence: GALNS NM_000512.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.151

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 16-88813738-G-C is Benign according to our data. Variant chr16-88813738-G-C is described in ClinVar as [Benign]. Clinvar id is 321168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNS	NM_000512.5	c.*701C>G		3_prime_UTR_variant	14/14	ENST00000268695.10	NP_000503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALNS	ENST00000268695.10	c.*701C>G		3_prime_UTR_variant	14/14	1	NM_000512.5	ENSP00000268695	P1
GALNS	ENST00000562593.5	n.5679C>G		non_coding_transcript_exon_variant	12/12	1
GALNS	ENST00000567525.5	c.*1741C>G		3_prime_UTR_variant, NMD_transcript_variant	12/12	2		ENSP00000454484

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33838 AN: 152094 Hom.: 4419 Cov.: 33

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.153 AC: 48 AN: 314 Hom.: 6 Cov.: 0 AF XY: 0.198 AC XY: 32 AN XY: 162

Gnomad4 AMR exome AF: 0.0556

Gnomad4 ASJ exome AF: 0.500

Gnomad4 SAS exome AF: 0.278

Gnomad4 NFE exome AF: 0.137

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.222 AC: 33844 AN: 152214 Hom.: 4418 Cov.: 33 AF XY: 0.225 AC XY: 16717 AN XY: 74418

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.267

Alfa AF: 0.236 Hom.: 584

Bravo AF: 0.221

Asia WGS AF: 0.318 AC: 1107 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Adenine phosphoribosyltransferase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Mucopolysaccharidosis, MPS-IV-A Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Morquio syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs77936719; hg19: chr16-88880146;