rs550640

Variant names:

• chrX-123394952-T-C
• rs550640
• NM_000828.5:c.751-16T>C

Your query was ambiguous. Multiple possible variants found:

• chrX-123394952-T-C
• chrX-123394952-T-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_007325.5(GRIA3):​c.751-16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (12181 hom., 18150 hem., cov: 22)
  • Exomes 𝑓: 0.59 (128079 hom. 186993 hem.)
  • Failed GnomAD Quality Control
• Consequence: GRIA3 NM_007325.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.588
• Publications: 16 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.73).
• BP6: Variant X-123394952-T-C is Benign according to our data. Variant chrX-123394952-T-C is described in ClinVar as Benign. ClinVar VariationId is 1285307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007325.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA3	NM_000828.5	MANE Plus Clinical	c.751-16T>C		intron	N/A	NP_000819.4	P42263-1
	GRIA3	NM_007325.5	MANE Select	c.751-16T>C		intron	N/A	NP_015564.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA3	ENST00000620443.2	TSL:1 MANE Select	c.751-16T>C		intron	N/A	ENSP00000478489.1	P42263-2
	GRIA3	ENST00000622768.5	TSL:5 MANE Plus Clinical	c.751-16T>C		intron	N/A	ENSP00000481554.1	P42263-1
	GRIA3	ENST00000620581.4	TSL:1	n.751-16T>C		intron	N/A	ENSP00000481875.1	A0A087WYJ6

Frequencies

GnomAD3 genomes AF: 0.554 AC: 61102 AN: 110242 Hom.: 12185 Cov.: 22

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.645

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.551

GnomAD2 exomes AF: 0.586 AC: 106779 AN: 182155 AF XY: 0.587

Gnomad AFR exome AF: 0.422

Gnomad AMR exome AF: 0.559

Gnomad ASJ exome AF: 0.639

Gnomad EAS exome AF: 0.603

Gnomad FIN exome AF: 0.739

Gnomad NFE exome AF: 0.613

Gnomad OTH exome AF: 0.603

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.592 AC: 612408 AN: 1035256 Hom.: 128079 Cov.: 22 AF XY: 0.582 AC XY: 186993 AN XY: 321216

African (AFR) AF: 0.424 AC: 10744 AN: 25320

American (AMR) AF: 0.557 AC: 19551 AN: 35084

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 12150 AN: 18994

East Asian (EAS) AF: 0.658 AC: 19680 AN: 29920

South Asian (SAS) AF: 0.460 AC: 24331 AN: 52843

European-Finnish (FIN) AF: 0.727 AC: 29448 AN: 40486

Middle Eastern (MID) AF: 0.604 AC: 2291 AN: 3791

European-Non Finnish (NFE) AF: 0.597 AC: 468735 AN: 784803

Other (OTH) AF: 0.579 AC: 25478 AN: 44015

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.554 AC: 61129 AN: 110296 Hom.: 12181 Cov.: 22 AF XY: 0.556 AC XY: 18150 AN XY: 32622

African (AFR) AF: 0.420 AC: 12738 AN: 30354

American (AMR) AF: 0.566 AC: 5846 AN: 10320

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 1704 AN: 2633

East Asian (EAS) AF: 0.629 AC: 2176 AN: 3462

South Asian (SAS) AF: 0.455 AC: 1175 AN: 2582

European-Finnish (FIN) AF: 0.730 AC: 4242 AN: 5809

Middle Eastern (MID) AF: 0.638 AC: 136 AN: 213

European-Non Finnish (NFE) AF: 0.603 AC: 31827 AN: 52749

Other (OTH) AF: 0.557 AC: 836 AN: 1500

Alfa AF: 0.586 Hom.: 29010

Bravo AF: 0.545

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Syndromic X-linked intellectual disability 94 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.86
PhyloP100		-0.59
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: rs550640; hg19: chrX-122528803; COSMIC: COSV52057354;