chr15-59618415-C-G

Variant names:

• chr15-59618415-C-G
• NM_004751.3:c.177C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004751.3(GCNT3):​c.177C>G​(p.Phe59Leu) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: GCNT3 NM_004751.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0560

Genes affected

GCNT3 (HGNC:4205): (glucosaminyl (N-acetyl) transferase 3, mucin type) This gene encodes a member of the N-acetylglucosaminyltransferase family. The encoded protein is a beta-6-N-acetylglucosamine-transferase that catalyzes the formation of core 2 and core 4 O-glycans on mucin-type glycoproteins.[provided by RefSeq, Apr 2009]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061628193).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCNT3	NM_004751.3	c.177C>G	p.Phe59Leu	missense_variant	Exon 3 of 3	ENST00000396065.3	NP_004742.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCNT3	ENST00000396065.3	c.177C>G	p.Phe59Leu	missense_variant	Exon 3 of 3	1	NM_004751.3	ENSP00000379377.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.177C>G (p.F59L) alteration is located in exon 3 (coding exon 1) of the GCNT3 gene. This alteration results from a C to G substitution at nucleotide position 177, causing the phenylalanine (F) at amino acid position 59 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	0.20
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.3
DANN	Benign	0.55
DEOGEN2	Benign	0.0098	T;T;T;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.56	T;.;T;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.062	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	.;N;N;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.17	N;N;N;N
REVEL	Benign	0.10
Sift	Benign	0.63	.;T;T;.
Sift4G	Benign	0.20	T;T;T;D
Polyphen		0.0	.;B;B;.
Vest4		0.029, 0.0050
MutPred		0.40		Loss of methylation at K61 (P = 0.1062);Loss of methylation at K61 (P = 0.1062);Loss of methylation at K61 (P = 0.1062);Loss of methylation at K61 (P = 0.1062);
MVP		0.18
ClinPred		0.037	T
GERP RS		4.3
Varity_R		0.085
gMVP		0.40

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: chr15-59910614;