12-103999400-C-A

Variant names:

• chr12-103999400-C-A
• rs375188988
• NM_001384711.1:c.399G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001384711.1(GLT8D2):​c.399G>T​(p.Gln133His) 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 benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GLT8D2 NM_001384711.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15897757).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384711.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLT8D2	NM_001384711.1	MANE Select	c.399G>T	p.Gln133His	missense	Exon 6 of 11	NP_001371640.1	Q9H1C3
	GLT8D2	NM_001384712.1		c.414G>T	p.Gln138His	missense	Exon 5 of 10	NP_001371641.1
	GLT8D2	NM_001316967.2		c.399G>T	p.Gln133His	missense	Exon 6 of 11	NP_001303896.1	Q9H1C3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLT8D2	ENST00000360814.9	TSL:1 MANE Select	c.399G>T	p.Gln133His	missense	Exon 6 of 11	ENSP00000354053.4	Q9H1C3
	GLT8D2	ENST00000951197.1		c.399G>T	p.Gln133His	missense	Exon 6 of 12	ENSP00000621256.1
	GLT8D2	ENST00000546436.5	TSL:5	c.399G>T	p.Gln133His	missense	Exon 5 of 10	ENSP00000449750.1	Q9H1C3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.70
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.45
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.12	N
PhyloP100		1.8
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.17	N
REVEL	Benign	0.075
Sift	Benign	0.28	T
Sift4G	Benign	0.33	T
Polyphen		0.0010	B
Vest4		0.24
MutPred		0.37		Gain of catalytic residue at L135 (P = 0.0211)
MVP		0.32
MPC		0.12
ClinPred		0.21	T
GERP RS		2.4
Varity_R		0.062
gMVP		0.72
Mutation Taster		=58/42	polymorphism

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

Other links and lift over

dbSNP: rs375188988; hg19: chr12-104393178;