rs7058062

Variant names:

• chrX-123262262-C-A
• rs7058062
• NM_000828.5:c.508+8720C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-123262262-C-A
• chrX-123262262-C-G
• chrX-123262262-C-T

Variant summary

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

The NM_007325.5(GRIA3):​c.508+8720C>A 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 0.61 (14625 hom., 20090 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: GRIA3 NM_007325.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.448
• 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=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA3	NM_000828.5	c.508+8720C>A		intron_variant	Intron 3 of 15	ENST00000622768.5	NP_000819.4
GRIA3	NM_007325.5	c.508+8720C>A		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+8720C>A		intron_variant	Intron 3 of 15	1	NM_007325.5	ENSP00000478489.1
GRIA3	ENST00000622768.5	c.508+8720C>A		intron_variant	Intron 3 of 15	5	NM_000828.5	ENSP00000481554.1
GRIA3	ENST00000620581.4	n.508+8720C>A		intron_variant	Intron 3 of 16	1		ENSP00000481875.1
ENSG00000307341	ENST00000825206.1	n.667+51583G>T		intron_variant	Intron 6 of 6

Frequencies

GnomAD3 genomes AF: 0.610 AC: 67123 AN: 110117 Hom.: 14623 Cov.: 23

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.612

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: 0.610 AC: 67163 AN: 110169 Hom.: 14625 Cov.: 23 AF XY: 0.618 AC XY: 20090 AN XY: 32517

African (AFR) AF: 0.487 AC: 14762 AN: 30282

American (AMR) AF: 0.690 AC: 7182 AN: 10403

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 1561 AN: 2627

East Asian (EAS) AF: 0.862 AC: 2992 AN: 3469

South Asian (SAS) AF: 0.807 AC: 2038 AN: 2526

European-Finnish (FIN) AF: 0.642 AC: 3731 AN: 5814

Middle Eastern (MID) AF: 0.617 AC: 132 AN: 214

European-Non Finnish (NFE) AF: 0.635 AC: 33448 AN: 52663

Other (OTH) AF: 0.617 AC: 923 AN: 1495

Alfa AF: 0.631 Hom.: 43410

Bravo AF: 0.609

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.50
PhyloP100		0.45
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: rs7058062; hg19: chrX-122396113;