3-52694853-T-C

Position:

• chr3-52694853-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018446.4(GLT8D1):​c.1108A>G​(p.Ile370Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000055 in 1,454,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: GLT8D1 NM_018446.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.361

Genes affected

GLT8D1 (HGNC:24870): (glycosyltransferase 8 domain containing 1) This gene encodes a member of the glycosyltransferase family. The specific function of this protein has not been determined. Alternative splicing results in multiple transcript variants of this gene [provided by RefSeq, May 2013]

GLT8D1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036572278).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLT8D1	NM_018446.4	c.1108A>G	p.Ile370Val	missense_variant	10/10	ENST00000266014.11	NP_060916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLT8D1	ENST00000266014.11	c.1108A>G	p.Ile370Val	missense_variant	10/10	1	NM_018446.4	ENSP00000266014.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000550 AC: 8 AN: 1454810 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 724340

Gnomad4 AFR exome AF: 0.0000300

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000452

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Amyotrophic lateral sclerosis Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Dept. of Medical Genetics, Telemark Hospital Trust, Telemark Hospital Trust

Jan 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	9.2
DANN	Benign	0.85
DEOGEN2	Benign	0.029	T;T;T;T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.37	.;.;.;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.037	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L;L;L;L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.14	N;N;N;N
REVEL	Benign	0.054
Sift	Benign	0.77	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	B;B;B;B
Vest4		0.057
MutPred		0.11		Gain of MoRF binding (P = 0.0954);Gain of MoRF binding (P = 0.0954);Gain of MoRF binding (P = 0.0954);Gain of MoRF binding (P = 0.0954);
MVP		0.15
ClinPred		0.075	T
GERP RS		0.27
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.035
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-52728869;