Variant chr14-69325962-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001168368.2(GALNT16):c.503C>T(p.Pro168Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000502 in 1,612,648 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000053 ( 1 hom. )

Consequence

GALNT16
NM_001168368.2 missense, splice_region

Scores

Splicing: ADA: 0.9915

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.46

Variant links:

Genes affected

GALNT16 (HGNC:23233): (polypeptide N-acetylgalactosaminyltransferase 16) Enables polypeptide N-acetylgalactosaminyltransferase activity. Involved in protein O-linked glycosylation via serine and protein O-linked glycosylation via threonine. Predicted to be located in Golgi membrane. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

GALNT16 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNT16	NM_001168368.2 linkuse as main transcript	c.503C>T	p.Pro168Leu	missense_variant, splice_region_variant	5/15	ENST00000448469.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNT16	ENST00000448469.8 linkuse as main transcript	c.503C>T	p.Pro168Leu	missense_variant, splice_region_variant	5/15	1	NM_001168368.2	P1	Q8N428-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000875

AC:

AN:

251404

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000534

AC:

AN:

1460450

Hom.:

Cov.:

AF XY:

0.0000633

AC XY:

AN XY:

726646

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000477

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000258

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 22, 2023

The c.503C>T (p.P168L) alteration is located in exon 5 (coding exon 5) of the GALNT16 gene. This alteration results from a C to T substitution at nucleotide position 503, causing the proline (P) at amino acid position 168 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;T;.

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.91

M_CAP

Benign

0.056

MetaRNN

Benign

0.39

T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.0

M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-7.0

D;D;D

REVEL

Benign

0.24

Sift

Uncertain

0.028

D;D;D

Sift4G

Benign

0.13

T;T;T

Polyphen

0.34

B;B;.

Vest4

0.51

MutPred

0.49

Gain of catalytic residue at L172 (P = 0.001);Gain of catalytic residue at L172 (P = 0.001);Gain of catalytic residue at L172 (P = 0.001);

MVP

0.62

MPC

0.36

ClinPred

0.12

GERP RS

5.7

Varity_R

0.27

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.80

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over