X-14530113-C-G

Variant names:

• chrX-14530113-C-G
• NM_002063.4:c.56C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002063.4(GLRA2):​c.56C>G​(p.Thr19Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000948 in 1,055,032 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.5e-7 (0 hom. 0 hem.)
• Consequence: GLRA2 NM_002063.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.72

Genes affected

GLRA2 (HGNC:4327): (glycine receptor alpha 2) The glycine receptor consists of two subunits, alpha and beta, and acts as a pentamer. The protein encoded by this gene is an alpha subunit and can bind strychnine. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRA2	NM_002063.4	c.56C>G	p.Thr19Arg	missense_variant	Exon 1 of 9	ENST00000218075.9	NP_002054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLRA2	ENST00000218075.9	c.56C>G	p.Thr19Arg	missense_variant	Exon 1 of 9	1	NM_002063.4	ENSP00000218075.4
GLRA2	ENST00000355020.9	c.56C>G	p.Thr19Arg	missense_variant	Exon 1 of 9	1		ENSP00000347123.4
GLRA2	ENST00000443437.6	n.56C>G		non_coding_transcript_exon_variant	Exon 2 of 11	2		ENSP00000387756.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.48e-7 AC: 1 AN: 1055032 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 325594

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: 0.00000125

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Feb 23, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (PMID: 25741868) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.30
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.31	T;.
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.54	D;D
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.23	N;N
REVEL	Uncertain	0.54
Sift	Benign	0.060	T;T
Sift4G	Benign	0.45	T;T
Polyphen		0.98	D;B
Vest4		0.49
MutPred		0.75		Gain of methylation at T19 (P = 0.0297);Gain of methylation at T19 (P = 0.0297);
MVP		0.99
MPC		1.3
ClinPred		0.57	D
GERP RS		5.5
Varity_R		0.51
gMVP		0.87

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-14548235;