12-103993487-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001384711.1(GLT8D2):c.785G>C(p.Ser262Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GLT8D2 NM_001384711.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.05

Genes affected

GLT8D2 (HGNC:24890): (glycosyltransferase 8 domain containing 2) Predicted to enable glycosyltransferase activity. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLT8D2	NM_001384711.1	c.785G>C	p.Ser262Thr	missense_variant	10/11	ENST00000360814.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLT8D2	ENST00000360814.9	c.785G>C	p.Ser262Thr	missense_variant	10/11	1	NM_001384711.1	P1
GLT8D2	ENST00000546436.5	c.785G>C	p.Ser262Thr	missense_variant	9/10	5		P1
GLT8D2	ENST00000548660.5	c.785G>C	p.Ser262Thr	missense_variant	10/11	2		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

Marfanoid habitus and intellectual disability Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Equipe Genetique des Anomalies du Developpement, Université de Bourgogne

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
Cadd	Pathogenic	26
Dann	Uncertain	0.98
DEOGEN2	Benign	0.19	T;T;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.43	T;T;T
Polyphen		0.98	D;D;D
Vest4		0.54
MutPred		0.50		Gain of catalytic residue at S262 (P = 0.0021);Gain of catalytic residue at S262 (P = 0.0021);Gain of catalytic residue at S262 (P = 0.0021);
MVP		0.37
MPC		0.49
ClinPred		0.92	D
GERP RS		5.6
Varity_R		0.32
gMVP		0.74

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

LitVar

Other links and lift over

dbSNP: rs1212627359; hg19: chr12-104387265;