dbSNP rs755181209: GRIA3:c.-1C>T (chrX-123184535-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_007325.5(GRIA3):c.-1C>T variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00000501 in 1,197,202 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 21)

Exomes 𝑓: 0.0000046 ( 0 hom. 2 hem. )

Consequence

GRIA3
NM_007325.5 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.04

Publications

0 publications found

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 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

GRIA3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BS2

High Hemizygotes in GnomAdExome4 at 2 XL gene

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GRIA3	NM_000828.5	MANE Plus Clinical	c.-1C>T	5_prime_UTR	Exon 1 of 16	NP_000819.4	P42263-1
GRIA3	NM_007325.5	MANE Select	c.-1C>T	5_prime_UTR	Exon 1 of 16	NP_015564.5
GRIA3	NM_001256743.2		c.-1C>T	5_prime_UTR	Exon 1 of 4	NP_001243672.1	Q5XKG2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GRIA3	ENST00000620443.2	TSL:1 MANE Select	c.-1C>T	5_prime_UTR	Exon 1 of 16	ENSP00000478489.1	P42263-2
GRIA3	ENST00000622768.5	TSL:5 MANE Plus Clinical	c.-1C>T	5_prime_UTR	Exon 1 of 16	ENSP00000481554.1	P42263-1
GRIA3	ENST00000611689.4	TSL:1	c.-1C>T	5_prime_UTR	Exon 1 of 4	ENSP00000478758.1	Q5XKG2

Frequencies

GnomAD3 genomes

AF:

0.00000904

AC:

AN:

110612

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0690

AC:

AN:

AF XY:

0.105

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0833

GnomAD4 exome

AF:

0.00000460

AC:

AN:

1086590

Hom.:

Cov.:

AF XY:

0.00000566

AC XY:

AN XY:

353162

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26174

American (AMR)

AF:

0.00

AC:

AN:

35191

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19300

East Asian (EAS)

AF:

0.00

AC:

AN:

30162

South Asian (SAS)

AF:

0.00

AC:

AN:

53899

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40531

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4103

European-Non Finnish (NFE)

AF:

0.00000601

AC:

AN:

831549

Other (OTH)

AF:

0.00

AC:

AN:

45681

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000904

AC:

AN:

110612

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32814

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30341

American (AMR)

AF:

0.00

AC:

AN:

10431

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2634

East Asian (EAS)

AF:

0.00

AC:

AN:

3484

South Asian (SAS)

AF:

0.00

AC:

AN:

2535

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5848

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

52954

Other (OTH)

AF:

0.00

AC:

AN:

1470

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

4.0

PromoterAI

-0.054

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over