3-52696251-T-C

Position:

• chr3-52696251-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_018446.4(GLT8D1):​c.515A>G​(p.Asp172Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GLT8D1 NM_018446.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.931

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLT8D1	NM_018446.4	c.515A>G	p.Asp172Gly	missense_variant	6/10	ENST00000266014.11	NP_060916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLT8D1	ENST00000266014.11	c.515A>G	p.Asp172Gly	missense_variant	6/10	1	NM_018446.4	ENSP00000266014.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Nov 20, 2024

The c.515A>G (p.D172G) alteration is located in exon 7 (coding exon 5) of the GLT8D1 gene. This alteration results from a A to G substitution at nucleotide position 515, causing the aspartic acid (D) at amino acid position 172 to be replaced by a glycine (G). 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	0.81
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D;D;D;D;.
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.97	.;.;.;D;D
M_CAP	Uncertain	0.091	D
MetaRNN	Pathogenic	0.93	D;D;D;D;D
MetaSVM	Benign	-0.40	T
MutationAssessor	Pathogenic	3.2	M;M;M;M;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-4.7	D;D;D;D;D
REVEL	Pathogenic	0.68
Sift	Uncertain	0.0070	D;D;D;D;D
Sift4G	Uncertain	0.016	D;D;D;D;.
Polyphen		1.0	D;D;D;D;.
Vest4		0.92
MutPred		0.82		Loss of stability (P = 0.0616);Loss of stability (P = 0.0616);Loss of stability (P = 0.0616);Loss of stability (P = 0.0616);Loss of stability (P = 0.0616);
MVP		0.72
ClinPred		1.0	D
GERP RS		6.1
Varity_R		0.92
gMVP		0.84

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: chr3-52730267;