rs3743544

Variant names:

• chr16-88837678-A-G
• rs3743544
• NM_000512.5:c.510T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-88837678-A-G
• chr16-88837678-A-T
• chr16-88837678-A-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.510T>C​(p.Tyr170Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0383 in 1,613,984 control chromosomes in the GnomAD database, including 1,423 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (150 hom., cov: 32)
  • Exomes 𝑓: 0.038 (1273 hom.)
• Consequence: GALNS NM_000512.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.141
• 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=-0.7).
• BP6: Variant 16-88837678-A-G is Benign according to our data. Variant chr16-88837678-A-G is described in ClinVar as Benign. ClinVar VariationId is 93180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0773 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.510T>C	p.Tyr170Tyr	synonymous	Exon 5 of 14	NP_000503.1	P34059
	GALNS	NM_001323544.2		c.528T>C	p.Tyr176Tyr	synonymous	Exon 6 of 15	NP_001310473.1
	GALNS	NM_001323543.2		c.-46T>C		5_prime_UTR	Exon 4 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.510T>C	p.Tyr170Tyr	synonymous	Exon 5 of 14	ENSP00000268695.5	P34059
	GALNS	ENST00000562593.5	TSL:1	n.3919T>C		non_coding_transcript_exon	Exon 3 of 12
	GALNS	ENST00000862787.1		c.621T>C	p.Tyr207Tyr	synonymous	Exon 6 of 15	ENSP00000532846.1

Frequencies

GnomAD3 genomes AF: 0.0388 AC: 5903 AN: 152114 Hom.: 149 Cov.: 32

Gnomad AFR AF: 0.0318

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0696

Gnomad ASJ AF: 0.0374

Gnomad EAS AF: 0.0313

Gnomad SAS AF: 0.0840

Gnomad FIN AF: 0.0192

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0357

Gnomad OTH AF: 0.0469

GnomAD2 exomes AF: 0.0457 AC: 11487 AN: 251426 AF XY: 0.0473

Gnomad AFR exome AF: 0.0323

Gnomad AMR exome AF: 0.0672

Gnomad ASJ exome AF: 0.0346

Gnomad EAS exome AF: 0.0352

Gnomad FIN exome AF: 0.0215

Gnomad NFE exome AF: 0.0391

Gnomad OTH exome AF: 0.0451

GnomAD4 exome AF: 0.0383 AC: 55960 AN: 1461752 Hom.: 1273 Cov.: 32 AF XY: 0.0395 AC XY: 28716 AN XY: 727178

African (AFR) AF: 0.0308 AC: 1030 AN: 33478

American (AMR) AF: 0.0656 AC: 2936 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 880 AN: 26136

East Asian (EAS) AF: 0.0422 AC: 1675 AN: 39698

South Asian (SAS) AF: 0.0786 AC: 6781 AN: 86250

European-Finnish (FIN) AF: 0.0227 AC: 1209 AN: 53350

Middle Eastern (MID) AF: 0.0570 AC: 328 AN: 5750

European-Non Finnish (NFE) AF: 0.0349 AC: 38813 AN: 1111972

Other (OTH) AF: 0.0382 AC: 2308 AN: 60394

GnomAD4 genome AF: 0.0389 AC: 5917 AN: 152232 Hom.: 150 Cov.: 32 AF XY: 0.0396 AC XY: 2945 AN XY: 74434

African (AFR) AF: 0.0319 AC: 1326 AN: 41544

American (AMR) AF: 0.0700 AC: 1070 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0374 AC: 130 AN: 3472

East Asian (EAS) AF: 0.0306 AC: 158 AN: 5170

South Asian (SAS) AF: 0.0840 AC: 405 AN: 4820

European-Finnish (FIN) AF: 0.0192 AC: 204 AN: 10620

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0357 AC: 2427 AN: 68006

Other (OTH) AF: 0.0478 AC: 101 AN: 2112

Alfa AF: 0.0365 Hom.: 71

Bravo AF: 0.0410

Asia WGS AF: 0.0710 AC: 248 AN: 3478

EpiCase AF: 0.0399

EpiControl AF: 0.0401

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.98
DANN	Benign	0.81
PhyloP100		-0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs3743544; hg19: chr16-88904086; COSMIC: COSV51938732; COSMIC: COSV51938732;