rs144022438

Variant names:

• chrX-14730298-C-G
• NM_002063.4:c.1172C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-14730298-C-G
• chrX-14730298-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002063.4(GLRA2):​c.1172C>G​(p.Ala391Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000913 in 1,095,093 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: GLRA2 NM_002063.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.08

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]

FANCB (HGNC:3583): (FA complementation group B) This gene encodes a member of the Fanconi anemia complementation group B. This protein is assembled into a nucleoprotein complex that is involved in the repair of DNA lesions. Mutations in this gene can cause chromosome instability and VACTERL syndrome with hydrocephalus. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07769808).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLRA2	NM_002063.4	c.1172C>G	p.Ala391Gly	missense_variant	Exon 9 of 9	ENST00000218075.9	NP_002054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLRA2	ENST00000218075.9	c.1172C>G	p.Ala391Gly	missense_variant	Exon 9 of 9	1	NM_002063.4	ENSP00000218075.4

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 9.13e-7 AC: 1 AN: 1095093 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 360537

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: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Benign	0.16
DEOGEN2	Benign	0.26	.;T;.
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.078	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.2	.;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.72	N;N;N
REVEL	Benign	0.18
Sift	Benign	0.93	T;T;T
Sift4G	Benign	0.41	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.16
MutPred		0.50		.;Gain of glycosylation at K390 (P = 0.108);Gain of glycosylation at K390 (P = 0.108);
MVP		0.62
MPC		1.1
ClinPred		0.19	T
GERP RS		3.7
Varity_R		0.11
gMVP		0.42

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-14748420;