12-128899243-G-A

Position:

• chr12-128899243-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_144669.3(GLT1D1):​c.331G>A​(p.Val111Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GLT1D1 NM_144669.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.82

Genes affected

GLT1D1 (HGNC:26483): (glycosyltransferase 1 domain containing 1) Predicted to enable glycosyltransferase activity. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29421198).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLT1D1	NM_144669.3	c.331G>A	p.Val111Ile	missense_variant	4/8	ENST00000281703.11	NP_653270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLT1D1	ENST00000281703.11	c.331G>A	p.Val111Ile	missense_variant	4/8	2	NM_144669.3	ENSP00000281703.6
GLT1D1	ENST00000442111.7	c.331G>A	p.Val111Ile	missense_variant	4/12	5		ENSP00000394692.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000225 Hom.: 0

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

Mar 25, 2024

The c.331G>A (p.V111I) alteration is located in exon 4 (coding exon 4) of the GLT1D1 gene. This alteration results from a G to A substitution at nucleotide position 331, causing the valine (V) at amino acid position 111 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	0.14
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.0091	T;.;.
Eigen	Benign	0.17
Eigen_PC	Benign	0.066
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.6	M;M;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.76	N;N;N
REVEL	Uncertain	0.34
Sift	Uncertain	0.0090	D;T;D
Sift4G	Benign	0.085	T;T;T
Polyphen		0.99, 0.83	.;D;P
Vest4		0.38
MutPred		0.47		.;.;Loss of methylation at R97 (P = 0.0862);
MVP		0.37
MPC		0.19
ClinPred		0.64	D
GERP RS		4.4
Varity_R		0.13
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs145677630; hg19: chr12-129383788;