12-128945327-T-C

Position:

• chr12-128945327-T-C

Variant summary

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

The NM_144669.3(GLT1D1):​c.377T>C​(p.Val126Ala) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GLT1D1 NM_144669.3 missense, splice_region
• Scores: Splicing: ADA: 0.1177
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.45

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=0.3082554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLT1D1	NM_001366886.1	c.617T>C	p.Val206Ala	missense_variant, splice_region_variant	9/12	ENST00000442111.7
GLT1D1	NR_159493.1	n.627T>C		splice_region_variant, non_coding_transcript_exon_variant	7/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLT1D1	ENST00000442111.7	c.617T>C	p.Val206Ala	missense_variant, splice_region_variant	9/12	5	NM_001366886.1	P1

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

Mar 01, 2023

The c.377T>C (p.V126A) alteration is located in exon 5 (coding exon 5) of the GLT1D1 gene. This alteration results from a T to C substitution at nucleotide position 377, causing the valine (V) at amino acid position 126 to be replaced by an alanine (A). 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	0.28
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T;.;.
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.79	T;T;T
M_CAP	Uncertain	0.092	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-0.33	T
MutationAssessor	Uncertain	2.1	M;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.4	N;N;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.012	D;D;D
Sift4G	Uncertain	0.011	D;T;D
Polyphen		1.0, 0.96	.;D;D
Vest4		0.24
MutPred		0.64		.;.;Gain of catalytic residue at V207 (P = 0);
MVP		0.44
MPC		0.31
ClinPred		0.83	D
GERP RS		4.9
Varity_R		0.18
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.12
dbscSNV1_RF	Benign	0.42
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

LitVar

Other links and lift over

dbSNP: rs752954124; hg19: chr12-129429872;