Variant chrX-123184519-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000828.5(GRIA3):c.-17T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000312 in 1,161,975 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 137 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., 6 hem., cov: 21)

Exomes 𝑓: 0.00032 ( 0 hom. 131 hem. )

Consequence

GRIA3
NM_000828.5 5_prime_UTR

Scores

Splicing: ADA: 0.01408

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.06

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant X-123184519-T-C is Benign according to our data. Variant chrX-123184519-T-C is described in ClinVar as [Benign]. Clinvar id is 1258859.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000235 (26/110433) while in subpopulation SAS AF= 0.000793 (2/2521). AF 95% confidence interval is 0.000265. There are 0 homozygotes in gnomad4. There are 6 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
GRIA3	NM_000828.5 linkuse as main transcript	c.-17T>C	5_prime_UTR_variant	1/16	ENST00000622768.5	NP_000819.4
GRIA3	NM_007325.5 linkuse as main transcript	c.-17T>C	5_prime_UTR_variant	1/16	ENST00000620443.2	NP_015564.5
GRIA3	NM_001256743.2 linkuse as main transcript	c.-17T>C	5_prime_UTR_variant	1/4		NP_001243672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIA3	ENST00000620443.2 linkuse as main transcript	c.-17T>C		5_prime_UTR_variant	1/16	1	NM_007325.5	ENSP00000478489	P4	P42263-2
GRIA3	ENST00000622768.5 linkuse as main transcript	c.-17T>C		5_prime_UTR_variant	1/16	5	NM_000828.5	ENSP00000481554	A1	P42263-1

Frequencies

GnomAD3 genomes

AF:

0.000236

AC:

AN:

110381

Hom.:

Cov.:

AF XY:

0.000184

AC XY:

AN XY:

32629

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000963

Gnomad ASJ

AF:

0.000380

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000791

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00427

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000487

AC:

AN:

162269

Hom.:

AF XY:

0.000678

AC XY:

AN XY:

54539

show subpopulations

Gnomad AFR exome

AF:

0.0000817

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00137

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000627

Gnomad OTH exome

AF:

0.000767

GnomAD4 exome

AF:

0.000320

AC:

337

AN:

1051542

Hom.:

Cov.:

AF XY:

0.000400

AC XY:

131

AN XY:

327206

show subpopulations

Gnomad4 AFR exome

AF:

0.000157

Gnomad4 AMR exome

AF:

0.000228

Gnomad4 ASJ exome

AF:

0.000210

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00124

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000283

Gnomad4 OTH exome

AF:

0.000449

GnomAD4 genome

AF:

0.000235

AC:

AN:

110433

Hom.:

Cov.:

AF XY:

0.000184

AC XY:

AN XY:

32691

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000961

Gnomad4 ASJ

AF:

0.000380

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000793

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000479

Hom.:

Bravo

AF:

0.000249

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.014

dbscSNV1_RF

Benign

0.15

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over