19-41999108-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_002088.5(GRIK5):​c.2706G>A​(p.Ala902Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000082 in 1,219,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A902A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 8.2e-7 ( 0 hom. )

Consequence

GRIK5
NM_002088.5 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.280
Variant links:
Genes affected
GRIK5 (HGNC:4583): (glutamate ionotropic receptor kainate type subunit 5) This gene encodes a protein that belongs to the glutamate-gated ionic channel family. Glutamate functions as the major excitatory neurotransmitter in the central nervous system through activation of ligand-gated ion channels and G protein-coupled membrane receptors. The protein encoded by this gene forms functional heteromeric kainate-preferring ionic channels with the subunits encoded by related gene family members. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP7
Synonymous conserved (PhyloP=-0.28 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GRIK5NM_002088.5 linkc.2706G>A p.Ala902Ala synonymous_variant Exon 20 of 20 ENST00000593562.6 NP_002079.3 Q16478-1
GRIK5XM_011526862.3 linkc.2709G>A p.Ala903Ala synonymous_variant Exon 20 of 20 XP_011525164.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GRIK5ENST00000593562.6 linkc.2706G>A p.Ala902Ala synonymous_variant Exon 20 of 20 5 NM_002088.5 ENSP00000470251.1 Q16478-1
GRIK5ENST00000262895.7 linkc.2706G>A p.Ala902Ala synonymous_variant Exon 19 of 19 1 ENSP00000262895.2 Q16478-1
GRIK5ENST00000454993.6 linkn.1583G>A non_coding_transcript_exon_variant Exon 9 of 9 1
GRIK5ENST00000602210.1 linkn.*135G>A downstream_gene_variant 2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
8.20e-7
AC:
1
AN:
1219542
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
596962
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000201
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.39
CADD
Benign
13
DANN
Benign
0.96

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.

Other links and lift over

dbSNP: rs782424418; hg19: chr19-42503260; API