chrX-123239256-C-T

Variant names:

• chrX-123239256-C-T
• rs989638
• NM_000828.5:c.269-14047C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000828.5(GRIA3):​c.269-14047C>T 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 0.76 (22829 hom., 23658 hem., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: GRIA3 NM_000828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199
• Publications: 4 publications found

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]

GRIA3 Gene-Disease associations (from GenCC):

• syndromic X-linked intellectual disability 94

  Inheritance: XL Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• X-linked intellectual disability due to GRIA3 anomalies

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000307341 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA3	NM_000828.5	c.269-14047C>T		intron_variant	Intron 2 of 15	ENST00000622768.5	NP_000819.4
GRIA3	NM_007325.5	c.269-14047C>T		intron_variant	Intron 2 of 15	ENST00000620443.2	NP_015564.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA3	ENST00000620443.2	c.269-14047C>T		intron_variant	Intron 2 of 15	1	NM_007325.5	ENSP00000478489.1
GRIA3	ENST00000622768.5	c.269-14047C>T		intron_variant	Intron 2 of 15	5	NM_000828.5	ENSP00000481554.1

Frequencies

GnomAD3 genomes AF: 0.757 AC: 82101 AN: 108480 Hom.: 22826 Cov.: 21

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.840

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.894

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.767

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: 0.757 AC: 82144 AN: 108530 Hom.: 22829 Cov.: 21 AF XY: 0.757 AC XY: 23658 AN XY: 31264

African (AFR) AF: 0.851 AC: 25640 AN: 30144

American (AMR) AF: 0.841 AC: 8581 AN: 10207

Ashkenazi Jewish (ASJ) AF: 0.741 AC: 1889 AN: 2549

East Asian (EAS) AF: 0.894 AC: 3066 AN: 3428

South Asian (SAS) AF: 0.815 AC: 1985 AN: 2435

European-Finnish (FIN) AF: 0.663 AC: 3747 AN: 5648

Middle Eastern (MID) AF: 0.759 AC: 145 AN: 191

European-Non Finnish (NFE) AF: 0.684 AC: 35410 AN: 51780

Other (OTH) AF: 0.770 AC: 1140 AN: 1480

Alfa AF: 0.715 Hom.: 46684

Bravo AF: 0.782

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.84
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs989638; hg19: chrX-122373107;