9-76503594-G-T

Position:

• chr9-76503594-G-T

Variant summary

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

The NM_001490.5(GCNT1):​c.1213G>T​(p.Asp405Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 5.02

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 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	c.1213G>T	p.Asp405Tyr	missense_variant	4/4	ENST00000376730.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCNT1	ENST00000376730.5	c.1213G>T	p.Asp405Tyr	missense_variant	4/4	1	NM_001490.5	P1
GCNT1	ENST00000442371.5	c.1213G>T	p.Asp405Tyr	missense_variant	3/3	1		P1
GCNT1	ENST00000444201.6	c.1213G>T	p.Asp405Tyr	missense_variant	3/3	1		P1
GCNT1	ENST00000648797.1	n.142-11934G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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 24, 2023

The c.1213G>T (p.D405Y) alteration is located in exon 3 (coding exon 1) of the GCNT1 gene. This alteration results from a G to T substitution at nucleotide position 1213, causing the aspartic acid (D) at amino acid position 405 to be replaced by a tyrosine (Y). 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	0.18
BayesDel_addAF	Benign	-0.0073	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T;T;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.74	T;.;.
M_CAP	Benign	0.0056	T
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.7	M;M;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Benign	0.14
Sift	Uncertain	0.0080	D;D;D
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		0.94	P;P;P
Vest4		0.58
MutPred		0.39		Gain of solvent accessibility (P = 0.1116);Gain of solvent accessibility (P = 0.1116);Gain of solvent accessibility (P = 0.1116);
MVP		0.55
MPC		1.1
ClinPred		0.97	D
GERP RS		5.3
Varity_R		0.24
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr9-79118510;