Variant 9-76503540-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001490.5(GCNT1):c.1159G>A(p.Asp387Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GCNT1
NM_001490.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.917

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCNT1	NM_001490.5 linkuse as main transcript	c.1159G>A	p.Asp387Asn	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.1159G>A	p.Asp387Asn	missense_variant	4/4	1	NM_001490.5	P1
GCNT1	ENST00000442371.5 linkuse as main transcript	c.1159G>A	p.Asp387Asn	missense_variant	3/3	1		P1
GCNT1	ENST00000444201.6 linkuse as main transcript	c.1159G>A	p.Asp387Asn	missense_variant	3/3	1		P1
GCNT1	ENST00000648797.1 linkuse as main transcript	n.142-11988G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727238

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

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

Oct 20, 2023

The c.1159G>A (p.D387N) alteration is located in exon 3 (coding exon 1) of the GCNT1 gene. This alteration results from a G to A substitution at nucleotide position 1159, causing the aspartic acid (D) at amino acid position 387 to be replaced by an asparagine (N). 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

Pathogenic

0.62

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.34

T;T;T

Eigen

Pathogenic

0.99

Eigen_PC

Pathogenic

0.95

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.97

D;.;.

M_CAP

Benign

0.041

MetaRNN

Pathogenic

0.92

D;D;D

MetaSVM

Benign

-0.82

MutationAssessor

Pathogenic

3.6

H;H;H

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-4.0

D;D;D

REVEL

Uncertain

0.45

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.90

MutPred

0.72

Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);

MVP

0.71

MPC

1.0

ClinPred

1.0

GERP RS

6.2

Varity_R

0.92

gMVP

0.93

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