Genetic Variant NM_000828.5:c.751-16T>C (chrX-123394952-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_000828.5(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_000828.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.588

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 -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 id is 1285307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-123394952-T-C is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIA3	NM_000828.5 link	c.751-16T>C		intron_variant	Intron 5 of 15	ENST00000622768.5	NP_000819.4	P42263-1Q17R51
GRIA3	NM_007325.5 link	c.751-16T>C		intron_variant	Intron 5 of 15	ENST00000620443.2	NP_015564.5	P42263-2Q17R51

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GRIA3	ENST00000620443.2 link	c.751-16T>C	intron_variant	Intron 5 of 15	1	NM_007325.5	ENSP00000478489.1	P42263-2
GRIA3	ENST00000622768.5 link	c.751-16T>C	intron_variant	Intron 5 of 15	5	NM_000828.5	ENSP00000481554.1	P42263-1
GRIA3	ENST00000620581.4 link	n.751-16T>C	intron_variant	Intron 5 of 16	1		ENSP00000481875.1	A0A087WYJ6

Frequencies

GnomAD3 genomes

AF:

0.554

AC:

61102

AN:

110242

Hom.:

12185

Cov.:

AF XY:

0.556

AC XY:

18116

AN XY:

32556

show subpopulations

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

GnomAD3 exomes

AF:

0.586

AC:

106779

AN:

182155

Hom.:

20075

AF XY:

0.587

AC XY:

39193

AN XY:

66719

show subpopulations

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 SAS exome

AF:

0.460

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.:

AF XY:

0.582

AC XY:

186993

AN XY:

321216

show subpopulations

Gnomad4 AFR exome

AF:

0.424

Gnomad4 AMR exome

AF:

0.557

Gnomad4 ASJ exome

AF:

0.640

Gnomad4 EAS exome

AF:

0.658

Gnomad4 SAS exome

AF:

0.460

Gnomad4 FIN exome

AF:

0.727

Gnomad4 NFE exome

AF:

0.597

Gnomad4 OTH exome

AF:

0.579

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.554

AC:

61129

AN:

110296

Hom.:

12181

Cov.:

AF XY:

0.556

AC XY:

18150

AN XY:

32622

show subpopulations

Gnomad4 AFR

AF:

0.420

Gnomad4 AMR

AF:

0.566

Gnomad4 ASJ

AF:

0.647

Gnomad4 EAS

AF:

0.629

Gnomad4 SAS

AF:

0.455

Gnomad4 FIN

AF:

0.730

Gnomad4 NFE

AF:

0.603

Gnomad4 OTH

AF:

0.557

Alfa

AF:

0.590

Hom.:

17710

Bravo

AF:

0.545

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Syndromic X-linked intellectual disability 94

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.86

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

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