16-88814143-T-C

Variant names:

• chr16-88814143-T-C
• rs79507351
• NM_000512.5:c.*296A>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.*296A>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 0.00794 in 507,384 control chromosomes in the GnomAD database, including 143 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (110 hom., cov: 33)
  • Exomes 𝑓: 0.0028 (33 hom.)
• Consequence: GALNS NM_000512.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.957
• 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=-0.92).
• BP6: Variant 16-88814143-T-C is Benign according to our data. Variant chr16-88814143-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 321177.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0671 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.*296A>G		3_prime_UTR	Exon 14 of 14	NP_000503.1	P34059
	GALNS	NM_001323544.2		c.*296A>G		3_prime_UTR	Exon 15 of 15	NP_001310473.1
	GALNS	NM_001323543.2		c.*296A>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.*296A>G		3_prime_UTR	Exon 14 of 14	ENSP00000268695.5	P34059
	GALNS	ENST00000562593.5	TSL:1	n.5274A>G		non_coding_transcript_exon	Exon 12 of 12
	GALNS	ENST00000862787.1		c.*296A>G		3_prime_UTR	Exon 15 of 15	ENSP00000532846.1

Frequencies

GnomAD3 genomes AF: 0.0199 AC: 3023 AN: 152148 Hom.: 108 Cov.: 33

Gnomad AFR AF: 0.0690

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00798

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.0158

GnomAD4 exome AF: 0.00279 AC: 991 AN: 355118 Hom.: 33 Cov.: 0 AF XY: 0.00238 AC XY: 444 AN XY: 186522

African (AFR) AF: 0.0712 AC: 741 AN: 10404

American (AMR) AF: 0.00609 AC: 95 AN: 15600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11040

East Asian (EAS) AF: 0.00 AC: 0 AN: 22656

South Asian (SAS) AF: 0.000275 AC: 12 AN: 43564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20376

Middle Eastern (MID) AF: 0.00259 AC: 4 AN: 1544

European-Non Finnish (NFE) AF: 0.000105 AC: 22 AN: 209388

Other (OTH) AF: 0.00569 AC: 117 AN: 20546

GnomAD4 genome AF: 0.0200 AC: 3040 AN: 152266 Hom.: 110 Cov.: 33 AF XY: 0.0194 AC XY: 1446 AN XY: 74460

African (AFR) AF: 0.0692 AC: 2876 AN: 41542

American (AMR) AF: 0.00791 AC: 121 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68008

Other (OTH) AF: 0.0156 AC: 33 AN: 2110

Alfa AF: 0.0188 Hom.: 13

Bravo AF: 0.0233

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Adenine phosphoribosyltransferase deficiency (1)
-	-	1	Morquio syndrome (1)
-	-	1	Mucopolysaccharidosis, MPS-IV-A (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.52
PhyloP100		-0.96
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: rs79507351; hg19: chr16-88880551;