3-52695285-C-A

Position:

• chr3-52695285-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018446.4(GLT8D1):​c.830G>T​(p.Arg277Ile) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GLT8D1 NM_018446.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.98

Genes affected

GLT8D1 (HGNC:24870): (glycosyltransferase 8 domain containing 1) This gene encodes a member of the glycosyltransferase family. The specific function of this protein has not been determined. Alternative splicing results in multiple transcript variants of this gene [provided by RefSeq, May 2013]

GLT8D1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.767

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLT8D1	NM_018446.4	c.830G>T	p.Arg277Ile	missense_variant	9/10	ENST00000266014.11	NP_060916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLT8D1	ENST00000266014.11	c.830G>T	p.Arg277Ile	missense_variant	9/10	1	NM_018446.4	ENSP00000266014.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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 23, 2023

The c.830G>T (p.R277I) alteration is located in exon 10 (coding exon 8) of the GLT8D1 gene. This alteration results from a G to T substitution at nucleotide position 830, causing the arginine (R) at amino acid position 277 to be replaced by an isoleucine (I). 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	0.33
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Benign	0.26	T;T;T;T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.97	.;.;.;D
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.77	D;D;D;D
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.3	M;M;M;M
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.3	N;N;N;N
REVEL	Benign	0.17
Sift	Benign	0.12	T;T;T;T
Sift4G	Benign	0.13	T;T;T;T
Polyphen		0.97	D;D;D;D
Vest4		0.60
MutPred		0.65		Loss of catalytic residue at R277 (P = 0.0469);Loss of catalytic residue at R277 (P = 0.0469);Loss of catalytic residue at R277 (P = 0.0469);Loss of catalytic residue at R277 (P = 0.0469);
MVP		0.58
ClinPred		0.95	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.47
gMVP		0.72

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: chr3-52729301;