12-103997484-C-T

Variant names:

• chr12-103997484-C-T
• rs543467029
• NM_001384711.1:c.454G>A

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.454G>A​(p.Val152Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,613,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: GLT8D2 NM_001384711.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.96
• 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=0.14537925).

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.454G>A	p.Val152Ile	missense	Exon 7 of 11	NP_001371640.1	Q9H1C3
	GLT8D2	NM_001384712.1		c.469G>A	p.Val157Ile	missense	Exon 6 of 10	NP_001371641.1
	GLT8D2	NM_001316967.2		c.454G>A	p.Val152Ile	missense	Exon 7 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.454G>A	p.Val152Ile	missense	Exon 7 of 11	ENSP00000354053.4	Q9H1C3
	GLT8D2	ENST00000951197.1		c.523G>A	p.Val175Ile	missense	Exon 8 of 12	ENSP00000621256.1
	GLT8D2	ENST00000546436.5	TSL:5	c.454G>A	p.Val152Ile	missense	Exon 6 of 10	ENSP00000449750.1	Q9H1C3

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251330 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000868

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 AF: 0.00000342 AC: 5 AN: 1461600 Hom.: 0 Cov.: 29 AF XY: 0.00000275 AC XY: 2 AN XY: 727132

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.000112 AC: 5 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111764

Other (OTH) AF: 0.00 AC: 0 AN: 60388

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000924279), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152302 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74478

African (AFR) AF: 0.00 AC: 0 AN: 41560

American (AMR) AF: 0.000261 AC: 4 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.093
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.89	L
PhyloP100		5.0
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.096
Sift	Benign	0.50	T
Sift4G	Benign	0.48	T
Polyphen		0.62	P
Vest4		0.34
MutPred		0.58		Gain of catalytic residue at E150 (P = 0.0032)
MVP		0.20
MPC		0.16
ClinPred		0.25	T
GERP RS		5.4
Varity_R		0.079
gMVP		0.55
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs543467029; hg19: chr12-104391262;