16-88856712-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000512.5(GALNS):c.120+46A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (98 hom., cov: 20)
  • Exomes 𝑓: 0.035 (168 hom.)
• Consequence: GALNS NM_000512.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.348

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]

TRAPPC2L (HGNC:30887): (trafficking protein particle complex subunit 2L) This gene encodes a protein that interacts with the tethering factor trafficking protein particle (TRAPP complex). TRAPP complexes mediate the contact between vescicles and target membranes, and thus, are involved in vescicle-mediated transport of proteins and lipids. The encoded protein is related to the X-linked trafficking protein particle complex 2. A related pseudogene is located on the X chromosome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 16-88856712-T-G is Benign according to our data. Variant chr16-88856712-T-G is described in ClinVar as [Benign]. Clinvar id is 1289536.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNS	NM_000512.5	c.120+46A>C		intron_variant		ENST00000268695.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNS	ENST00000268695.10	c.120+46A>C		intron_variant		1	NM_000512.5	P1

Frequencies

GnomAD3 genomes AF: 0.0349 AC: 4449 AN: 127420 Hom.: 97 Cov.: 20

Gnomad AFR AF: 0.0562

Gnomad AMI AF: 0.0174

Gnomad AMR AF: 0.0263

Gnomad ASJ AF: 0.0136

Gnomad EAS AF: 0.0220

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.0409

Gnomad MID AF: 0.0106

Gnomad NFE AF: 0.0275

Gnomad OTH AF: 0.0356

GnomAD3 exomes AF: 0.0304 AC: 1357 AN: 44702 Hom.: 15 AF XY: 0.0302 AC XY: 706 AN XY: 23406

Gnomad AFR exome AF: 0.0584

Gnomad AMR exome AF: 0.0244

Gnomad ASJ exome AF: 0.0184

Gnomad EAS exome AF: 0.0265

Gnomad SAS exome AF: 0.0163

Gnomad FIN exome AF: 0.0408

Gnomad NFE exome AF: 0.0324

Gnomad OTH exome AF: 0.0308

GnomAD4 exome AF: 0.0346 AC: 10393 AN: 300556 Hom.: 168 Cov.: 3 AF XY: 0.0326 AC XY: 5243 AN XY: 160980

Gnomad4 AFR exome AF: 0.0721

Gnomad4 AMR exome AF: 0.0218

Gnomad4 ASJ exome AF: 0.0199

Gnomad4 EAS exome AF: 0.0269

Gnomad4 SAS exome AF: 0.0142

Gnomad4 FIN exome AF: 0.0559

Gnomad4 NFE exome AF: 0.0381

Gnomad4 OTH exome AF: 0.0427

GnomAD4 genome AF: 0.0350 AC: 4459 AN: 127502 Hom.: 98 Cov.: 20 AF XY: 0.0349 AC XY: 2136 AN XY: 61196

Gnomad4 AFR AF: 0.0564

Gnomad4 AMR AF: 0.0263

Gnomad4 ASJ AF: 0.0136

Gnomad4 EAS AF: 0.0216

Gnomad4 SAS AF: 0.0143

Gnomad4 FIN AF: 0.0409

Gnomad4 NFE AF: 0.0274

Gnomad4 OTH AF: 0.0353

Alfa AF: 0.0303 Hom.: 15

Bravo AF: 0.0330

Asia WGS AF: 0.0160 AC: 52 AN: 3218

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 19, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	5.4
Dann	Benign	0.66

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: rs534472993; hg19: chr16-88923120;