9-76502760-A-C

Position:

• chr9-76502760-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001490.5(GCNT1):​c.379A>C​(p.Ile127Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GCNT1 NM_001490.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.948

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.088478744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCNT1	NM_001490.5	c.379A>C	p.Ile127Leu	missense_variant	4/4	ENST00000376730.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCNT1	ENST00000376730.5	c.379A>C	p.Ile127Leu	missense_variant	4/4	1	NM_001490.5	P1
GCNT1	ENST00000442371.5	c.379A>C	p.Ile127Leu	missense_variant	3/3	1		P1
GCNT1	ENST00000444201.6	c.379A>C	p.Ile127Leu	missense_variant	3/3	1		P1
GCNT1	ENST00000648797.1	n.142-12768A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.379A>C (p.I127L) alteration is located in exon 3 (coding exon 1) of the GCNT1 gene. This alteration results from a A to C substitution at nucleotide position 379, causing the isoleucine (I) at amino acid position 127 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	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.51
DEOGEN2	Benign	0.047	T;T;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.55
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.65	T;.;.
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.088	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L;L
MutationTaster	Benign	0.60	N;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.39	N;N;N
REVEL	Benign	0.073
Sift	Benign	0.81	T;T;T
Sift4G	Benign	0.87	T;T;T
Polyphen		0.0010	B;B;B
Vest4		0.26
MutPred		0.56		Loss of methylation at K132 (P = 0.0597);Loss of methylation at K132 (P = 0.0597);Loss of methylation at K132 (P = 0.0597);
MVP		0.17
MPC		0.48
ClinPred		0.16	T
GERP RS		2.4
Varity_R		0.088
gMVP		0.60

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.

Other links and lift over

hg19: chr9-79117676;