X-123449072-T-C

Position:

• chrX-123449072-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000828.5(GRIA3):​c.2077-15793T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.52 (10650 hom., 16710 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: GRIA3 NM_000828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.977

Genes affected

GRIA3 (HGNC:4573): (glutamate ionotropic receptor AMPA type subunit 3) Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. These receptors are heteromeric protein complexes composed of multiple subunits, arranged to form ligand-gated ion channels. The classification of glutamate receptors is based on their activation by different pharmacologic agonists. The subunit encoded by this gene belongs to a family of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate)-sensitive glutamate receptors, and is subject to RNA editing (AGA->GGA; R->G). Alternative splicing at this locus results in different isoforms, which may vary in their signal transduction properties. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIA3	NM_000828.5	c.2077-15793T>C		intron_variant		ENST00000622768.5	NP_000819.4
GRIA3	NM_007325.5	c.2077-15793T>C		intron_variant		ENST00000620443.2	NP_015564.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIA3	ENST00000620443.2	c.2077-15793T>C		intron_variant		1	NM_007325.5	ENSP00000478489	P4
GRIA3	ENST00000622768.5	c.2077-15793T>C		intron_variant		5	NM_000828.5	ENSP00000481554	A1
GRIA3	ENST00000620581.4	c.2077-15793T>C		intron_variant, NMD_transcript_variant		1		ENSP00000481875

Frequencies

GnomAD3 genomes AF: 0.520 AC: 57329 AN: 110169 Hom.: 10660 Cov.: 22 AF XY: 0.514 AC XY: 16676 AN XY: 32473

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.531

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.520 AC: 57344 AN: 110226 Hom.: 10650 Cov.: 22 AF XY: 0.514 AC XY: 16710 AN XY: 32540

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.556

Gnomad4 ASJ AF: 0.566

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.525

Alfa AF: 0.529 Hom.: 62022

Bravo AF: 0.525

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.52
DANN	Benign	0.73

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

Other links and lift over

dbSNP: rs5911622; hg19: chrX-122582923; COSMIC: COSV52062156;