Variant 9-76502866-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001490.5(GCNT1):c.485A>G(p.Tyr162Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

GCNT1
NM_001490.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.34

Variant links:

Genes affected

GCNT1 (HGNC:4203): (glucosaminyl (N-acetyl) transferase 1) This gene is a member of the beta-1,6-N-acetylglucosaminyltransferase gene family. It is essential to the formation of Gal beta 1-3(GlcNAc beta 1-6)GalNAc structures and the core 2 O-glycan branch. The gene coding this enzyme was originally mapped to 9q21, but was later localized to 9q13. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

GCNT1 links:

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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
GCNT1	NM_001490.5 linkuse as main transcript	c.485A>G	p.Tyr162Cys	missense_variant	4/4	ENST00000376730.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GCNT1	ENST00000376730.5 linkuse as main transcript	c.485A>G	p.Tyr162Cys	missense_variant	4/4	1	NM_001490.5	P1
GCNT1	ENST00000442371.5 linkuse as main transcript	c.485A>G	p.Tyr162Cys	missense_variant	3/3	1		P1
GCNT1	ENST00000444201.6 linkuse as main transcript	c.485A>G	p.Tyr162Cys	missense_variant	3/3	1		P1
GCNT1	ENST00000648797.1 linkuse as main transcript	n.142-12662A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461814

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Apr 09, 2024

The c.485A>G (p.Y162C) alteration is located in exon 3 (coding exon 1) of the GCNT1 gene. This alteration results from a A to G substitution at nucleotide position 485, causing the tyrosine (Y) at amino acid position 162 to be replaced by a cysteine (C). 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

0.30

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.39

T;T;T

Eigen

Benign

0.035

Eigen_PC

Benign

0.054

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.82

T;.;.

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.71

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L;L

MutationTaster

Benign

0.69

N;N;N;N

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-4.7

D;D;D

REVEL

Benign

0.22

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.85

P;P;P

Vest4

0.31

MutPred

0.79

Gain of catalytic residue at L163 (P = 0.0143);Gain of catalytic residue at L163 (P = 0.0143);Gain of catalytic residue at L163 (P = 0.0143);

MVP

0.35

MPC

1.0

ClinPred

1.0

GERP RS

4.9

Varity_R

0.76

gMVP

0.74

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over