12-103993487-C-A

Variant names:

• chr12-103993487-C-A
• rs1212627359
• NM_001384711.1:c.785G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001384711.1(GLT8D2):​c.785G>T​(p.Ser262Ile) variant causes a missense change. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S262T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GLT8D2 NM_001384711.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.05
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.824

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.785G>T	p.Ser262Ile	missense	Exon 10 of 11	NP_001371640.1	Q9H1C3
	GLT8D2	NM_001384712.1		c.800G>T	p.Ser267Ile	missense	Exon 9 of 10	NP_001371641.1
	GLT8D2	NM_001316967.2		c.785G>T	p.Ser262Ile	missense	Exon 10 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.785G>T	p.Ser262Ile	missense	Exon 10 of 11	ENSP00000354053.4	Q9H1C3
	GLT8D2	ENST00000951197.1		c.854G>T	p.Ser285Ile	missense	Exon 11 of 12	ENSP00000621256.1
	GLT8D2	ENST00000546436.5	TSL:5	c.785G>T	p.Ser262Ile	missense	Exon 9 of 10	ENSP00000449750.1	Q9H1C3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 241156 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.0
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.18
Sift	Benign	0.066	T
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.82
MutPred		0.55		Loss of disorder (P = 6e-04)
MVP		0.47
MPC		0.61
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.62
gMVP		0.84
Mutation Taster		=34/66	disease causing

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: rs1212627359; hg19: chr12-104387265;