16-88842710-C-T

Variant names:

• chr16-88842710-C-T
• rs11865929
• NM_000512.5:c.240G>A

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.240G>A​(p.Ser80Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00298 in 1,612,542 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S80S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.016 (51 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (68 hom.)
• Consequence: GALNS NM_000512.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -3.55
• 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=-0.56).
• BP6: Variant 16-88842710-C-T is Benign according to our data. Variant chr16-88842710-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 321207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0543 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.240G>A	p.Ser80Ser	synonymous	Exon 2 of 14	NP_000503.1	P34059
	GALNS	NM_001323544.2		c.258G>A	p.Ser86Ser	synonymous	Exon 3 of 15	NP_001310473.1
	GALNS	NM_001323543.2		c.-311-739G>A		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.240G>A	p.Ser80Ser	synonymous	Exon 2 of 14	ENSP00000268695.5	P34059
	GALNS	ENST00000562593.5	TSL:1	n.2915G>A		non_coding_transcript_exon	Exon 1 of 12
	GALNS	ENST00000565364.1	TSL:1	n.375G>A		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 2436 AN: 152194 Hom.: 51 Cov.: 33

Gnomad AFR AF: 0.0564

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00511

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00398 AC: 984 AN: 247370 AF XY: 0.00284

Gnomad AFR exome AF: 0.0564

Gnomad AMR exome AF: 0.00204

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000134

Gnomad OTH exome AF: 0.00133

GnomAD4 exome AF: 0.00162 AC: 2367 AN: 1460230 Hom.: 68 Cov.: 33 AF XY: 0.00137 AC XY: 997 AN XY: 726324

African (AFR) AF: 0.0577 AC: 1929 AN: 33452

American (AMR) AF: 0.00227 AC: 101 AN: 44586

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.000233 AC: 20 AN: 85984

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52720

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5766

European-Non Finnish (NFE) AF: 0.0000594 AC: 66 AN: 1111616

Other (OTH) AF: 0.00401 AC: 242 AN: 60344

GnomAD4 genome AF: 0.0160 AC: 2436 AN: 152312 Hom.: 51 Cov.: 33 AF XY: 0.0157 AC XY: 1167 AN XY: 74458

African (AFR) AF: 0.0562 AC: 2337 AN: 41566

American (AMR) AF: 0.00510 AC: 78 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

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

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68034

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00626 Hom.: 16

Bravo AF: 0.0177

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000594

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Mucopolysaccharidosis, MPS-IV-A (3)
-	-	2	not provided (2)
-	-	1	GALNS-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	1.9
DANN	Benign	0.77
PhyloP100		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=99/1	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: rs11865929; hg19: chr16-88909118;