16-88856744-C-T

Variant names:

• chr16-88856744-C-T
• rs368397682
• NM_000512.5:c.120+14G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_000512.5(GALNS):​c.120+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000634 in 1,499,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00010 (0 hom., cov: 27)
  • Exomes 𝑓: 0.000059 (0 hom.)
• Consequence: GALNS NM_000512.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0680
• 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, Labcorp Genetics (formerly Invitae), Ambry Genetics

LOC107983950 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 16-88856744-C-T is Benign according to our data. Variant chr16-88856744-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1594462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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+14G>A		intron	N/A	NP_000503.1	P34059
	GALNS	NM_001323544.2		c.-33+14G>A		intron	N/A	NP_001310473.1
	GALNS	NM_001323543.2		c.-312+14G>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.120+14G>A		intron	N/A	ENSP00000268695.5	P34059
	GALNS	ENST00000568311.1	TSL:1	c.120+14G>A		intron	N/A	ENSP00000455006.1	H3BNU2
	TRAPPC2L	ENST00000564365.5	TSL:1	c.-398+498C>T		intron	N/A	ENSP00000455447.1	H3BPS1

Frequencies

GnomAD3 genomes AF: 0.000101 AC: 15 AN: 148910 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.000174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00100

Gnomad SAS AF: 0.000433

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000489

GnomAD2 exomes AF: 0.000171 AC: 22 AN: 128318 AF XY: 0.000184

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00144

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000259

GnomAD4 exome AF: 0.0000592 AC: 80 AN: 1350240 Hom.: 0 Cov.: 28 AF XY: 0.0000677 AC XY: 45 AN XY: 664748

African (AFR) AF: 0.0000331 AC: 1 AN: 30166

American (AMR) AF: 0.00 AC: 0 AN: 33876

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24022

East Asian (EAS) AF: 0.000749 AC: 26 AN: 34704

South Asian (SAS) AF: 0.000311 AC: 24 AN: 77174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3978

European-Non Finnish (NFE) AF: 0.00000378 AC: 4 AN: 1057066

Other (OTH) AF: 0.000446 AC: 25 AN: 56074

GnomAD4 genome AF: 0.000101 AC: 15 AN: 149016 Hom.: 0 Cov.: 27 AF XY: 0.0000687 AC XY: 5 AN XY: 72772

African (AFR) AF: 0.000173 AC: 7 AN: 40432

American (AMR) AF: 0.00 AC: 0 AN: 15072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.00100 AC: 5 AN: 4978

South Asian (SAS) AF: 0.000433 AC: 2 AN: 4618

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66946

Other (OTH) AF: 0.000484 AC: 1 AN: 2064

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000869

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Mucopolysaccharidosis, MPS-IV-A (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	9.8
DANN	Benign	0.96
PhyloP100		-0.068
PromoterAI		-0.00040	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: rs368397682; hg19: chr16-88923152;