chrX-123270504-C-T

Variant names:

• chrX-123270504-C-T
• rs17330407
• NM_000828.5:c.508+16962C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000828.5(GRIA3):​c.508+16962C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0666 in 112,044 control chromosomes in the GnomAD database, including 327 homozygotes. There are 2,318 hemizygotes in GnomAD. 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 0.067 (327 hom., 2318 hem., cov: 23)
• Consequence: GRIA3 NM_000828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.483
• Publications: 0 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA3	NM_000828.5	c.508+16962C>T		intron_variant	Intron 3 of 15	ENST00000622768.5	NP_000819.4
GRIA3	NM_007325.5	c.508+16962C>T		intron_variant	Intron 3 of 15	ENST00000620443.2	NP_015564.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIA3	ENST00000620443.2	c.508+16962C>T		intron_variant	Intron 3 of 15	1	NM_007325.5	ENSP00000478489.1
GRIA3	ENST00000622768.5	c.508+16962C>T		intron_variant	Intron 3 of 15	5	NM_000828.5	ENSP00000481554.1
GRIA3	ENST00000620581.4	n.508+16962C>T		intron_variant	Intron 3 of 16	1		ENSP00000481875.1
ENSG00000307341	ENST00000825206.1	n.667+43341G>A		intron_variant	Intron 6 of 6

Frequencies

GnomAD3 genomes AF: 0.0665 AC: 7444 AN: 111988 Hom.: 326 Cov.: 23

Gnomad AFR AF: 0.0924

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.0983

Gnomad ASJ AF: 0.0629

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0494

Gnomad MID AF: 0.0335

Gnomad NFE AF: 0.0271

Gnomad OTH AF: 0.0656

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

GnomAD4 genome AF: 0.0666 AC: 7462 AN: 112044 Hom.: 327 Cov.: 23 AF XY: 0.0677 AC XY: 2318 AN XY: 34260

African (AFR) AF: 0.0924 AC: 2854 AN: 30894

American (AMR) AF: 0.0986 AC: 1044 AN: 10584

Ashkenazi Jewish (ASJ) AF: 0.0629 AC: 167 AN: 2655

East Asian (EAS) AF: 0.331 AC: 1158 AN: 3499

South Asian (SAS) AF: 0.137 AC: 367 AN: 2686

European-Finnish (FIN) AF: 0.0494 AC: 302 AN: 6116

Middle Eastern (MID) AF: 0.0321 AC: 7 AN: 218

European-Non Finnish (NFE) AF: 0.0271 AC: 1440 AN: 53197

Other (OTH) AF: 0.0734 AC: 111 AN: 1512

Alfa AF: 0.0563 Hom.: 1618

Bravo AF: 0.0757

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.56
DANN	Benign	0.46
PhyloP100		-0.48
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: rs17330407; hg19: chrX-122404355;