Variant 4-174788932-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006529.4(GLRA3):c.83C>T(p.Thr28Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000489 in 1,432,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000049 ( 0 hom. )

Consequence

GLRA3
NM_006529.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.58

Variant links:

Genes affected

GLRA3 (HGNC:4328): (glycine receptor alpha 3) This gene encodes a member of the ligand-gated ion channel protein family. The encoded protein is a member of the glycine receptor subfamily. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

GLRA3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2723319).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLRA3	NM_006529.4 linkuse as main transcript	c.83C>T	p.Thr28Ile	missense_variant	2/10	ENST00000274093.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLRA3	ENST00000274093.8 linkuse as main transcript	c.83C>T	p.Thr28Ile	missense_variant	2/10	1	NM_006529.4		O75311-1
GLRA3	ENST00000340217.5 linkuse as main transcript	c.83C>T	p.Thr28Ile	missense_variant	2/9	1		P1	O75311-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000132

AC:

AN:

227126

Hom.:

AF XY:

0.0000163

AC XY:

AN XY:

122932

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000282

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000489

AC:

AN:

1432874

Hom.:

Cov.:

AF XY:

0.00000561

AC XY:

AN XY:

712562

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000637

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 22, 2021

The c.83C>T (p.T28I) alteration is located in exon 2 (coding exon 2) of the GLRA3 gene. This alteration results from a C to T substitution at nucleotide position 83, causing the threonine (T) at amino acid position 28 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.026

BayesDel_noAF

Benign

-0.26

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.20

T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

0.095

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.20

Sift

Uncertain

0.016

D;D

Sift4G

Benign

0.18

T;T

Polyphen

0.078

B;B

Vest4

0.73

MutPred

0.36

Loss of glycosylation at T28 (P = 0.0057);Loss of glycosylation at T28 (P = 0.0057);

MVP

0.77

MPC

0.21

ClinPred

0.39

GERP RS

5.0

Varity_R

0.33

gMVP

0.48

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over