ENST00000620581.4:n.-2G>C

Variant names:

• chrX-123184369-G-C
• NM_000828.5:c.-167G>C

Variant summary

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

The ENST00000620581.4(GRIA3):​n.-167G>C variant causes a upstream gene 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: not found (cov: 20)
• Consequence: GRIA3 ENST00000620581.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000620581.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA3	NM_000828.5	MANE Plus Clinical	c.-167G>C		5_prime_UTR	Exon 1 of 16	NP_000819.4
	GRIA3	NM_007325.5	MANE Select	c.-167G>C		5_prime_UTR	Exon 1 of 16	NP_015564.5
	GRIA3	NM_001256743.2		c.-167G>C		5_prime_UTR	Exon 1 of 4	NP_001243672.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRIA3	ENST00000620443.2	TSL:1 MANE Select	c.-167G>C		5_prime_UTR	Exon 1 of 16	ENSP00000478489.1
	GRIA3	ENST00000622768.5	TSL:5 MANE Plus Clinical	c.-167G>C		5_prime_UTR	Exon 1 of 16	ENSP00000481554.1
	GRIA3	ENST00000611689.4	TSL:1	c.-167G>C		5_prime_UTR	Exon 1 of 4	ENSP00000478758.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 3

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	15
DANN	Benign	0.70
PhyloP100		0.33
PromoterAI		0.29	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chrX-122318222;