X-152652814-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018558.4(GABRQ):c.1432A>T(p.Ile478Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 1,207,414 control chromosomes in the GnomAD database, including 79,082 homozygotes. There are 175,185 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 6/7 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.48 (9130 hom., 15686 hem., cov: 23)
  • Exomes 𝑓: 0.43 (69952 hom. 159499 hem.)
• Consequence: GABRQ NM_018558.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.649

Genes affected

GABRQ (HGNC:14454): (gamma-aminobutyric acid type A receptor subunit theta) The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes the theta subunit of the GABA A receptor. The gene is mapped to chromosome Xq28 in a cluster of genes including those that encode the alpha 3 and epsilon subunits of the GABA A receptor. [provided by RefSeq, Jul 2017]

MAGEA3-DT (HGNC:56247): (MAGEA3 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0052278936).
• BP6: Variant X-152652814-A-T is Benign according to our data. Variant chrX-152652814-A-T is described in ClinVar as [Benign]. Clinvar id is 769197.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRQ	NM_018558.4	c.1432A>T	p.Ile478Phe	missense_variant	9/9	ENST00000598523.3
MAGEA3-DT	XR_938525.3	n.157-13020T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRQ	ENST00000598523.3	c.1432A>T	p.Ile478Phe	missense_variant	9/9	1	NM_018558.4	P1
MAGEA3-DT	ENST00000671457.1	n.130-13020T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.476 AC: 52522 AN: 110422 Hom.: 9134 Cov.: 23 AF XY: 0.476 AC XY: 15636 AN XY: 32852

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.397

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.445

GnomAD4 exome AF: 0.434 AC: 475617 AN: 1096943 Hom.: 69952 Cov.: 34 AF XY: 0.440 AC XY: 159499 AN XY: 362513

Gnomad4 AFR exome AF: 0.614

Gnomad4 AMR exome AF: 0.307

Gnomad4 ASJ exome AF: 0.370

Gnomad4 EAS exome AF: 0.681

Gnomad4 SAS exome AF: 0.552

Gnomad4 FIN exome AF: 0.455

Gnomad4 NFE exome AF: 0.416

Gnomad4 OTH exome AF: 0.455

GnomAD4 genome AF: 0.476 AC: 52558 AN: 110471 Hom.: 9130 Cov.: 23 AF XY: 0.477 AC XY: 15686 AN XY: 32913

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.447

Alfa AF: 0.574 Hom.: 5585

Bravo AF: 0.472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.52
MetaRNN	Benign	0.0052	T
Sift4G	Uncertain	0.027	D
Vest4		0.071
gMVP		0.16

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3810651; hg19: chrX-151821277;