16-88856712-T-G

Variant names:

• chr16-88856712-T-G
• rs534472993
• NM_000512.5:c.120+46A>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.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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.348
• Publications: 0 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]

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]

TRAPPC2L Gene-Disease associations (from GenCC):

• encephalopathy, progressive, early-onset, with episodic rhabdomyolysis

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

LOC107983950 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1289536.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.120+46A>C		intron	N/A	NP_000503.1	P34059
	GALNS	NM_001323544.2		c.-33+46A>C		intron	N/A	NP_001310473.1
	GALNS	NM_001323543.2		c.-312+46A>C		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.120+46A>C		intron	N/A	ENSP00000268695.5	P34059
	GALNS	ENST00000568311.1	TSL:1	c.120+46A>C		intron	N/A	ENSP00000455006.1	H3BNU2
	TRAPPC2L	ENST00000564365.5	TSL:1	c.-398+466T>G		intron	N/A	ENSP00000455447.1	H3BPS1

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

GnomAD2 exomes AF: 0.0304 AC: 1357 AN: 44702 AF XY: 0.0302

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 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

African (AFR) AF: 0.0721 AC: 613 AN: 8504

American (AMR) AF: 0.0218 AC: 325 AN: 14896

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 170 AN: 8554

East Asian (EAS) AF: 0.0269 AC: 420 AN: 15608

South Asian (SAS) AF: 0.0142 AC: 653 AN: 45986

European-Finnish (FIN) AF: 0.0559 AC: 878 AN: 15702

Middle Eastern (MID) AF: 0.0169 AC: 19 AN: 1126

European-Non Finnish (NFE) AF: 0.0381 AC: 6616 AN: 173796

Other (OTH) AF: 0.0427 AC: 699 AN: 16384

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

African (AFR) AF: 0.0564 AC: 1919 AN: 34014

American (AMR) AF: 0.0263 AC: 334 AN: 12708

Ashkenazi Jewish (ASJ) AF: 0.0136 AC: 42 AN: 3082

East Asian (EAS) AF: 0.0216 AC: 91 AN: 4208

South Asian (SAS) AF: 0.0143 AC: 53 AN: 3698

European-Finnish (FIN) AF: 0.0409 AC: 311 AN: 7600

Middle Eastern (MID) AF: 0.0117 AC: 3 AN: 256

European-Non Finnish (NFE) AF: 0.0274 AC: 1629 AN: 59346

Other (OTH) AF: 0.0353 AC: 63 AN: 1784

Alfa AF: 0.0303 Hom.: 15

Bravo AF: 0.0330

Asia WGS AF: 0.0160 AC: 52 AN: 3218

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.4
DANN	Benign	0.66
PhyloP100		0.35
PromoterAI		-0.017	Neutral
Mutation Taster		=100/0	polymorphism

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: rs534472993; hg19: chr16-88923120;