Variant rs689730 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_000835.6(GRIN2C):c.99C>T(p.Ala33=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,607,346 control chromosomes in the GnomAD database, including 12,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.14 ( 1791 hom., cov: 33)

Exomes 𝑓: 0.11 ( 10701 hom. )

Consequence

GRIN2C
NM_000835.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.419

Variant links:

Genes affected

GRIN2C (HGNC:4587): (glutamate ionotropic receptor NMDA type subunit 2C) This gene encodes a subunit of the N-methyl-D-aspartate (NMDA) receptor, which is a subtype of ionotropic glutamate receptor. NMDA receptors are found in the central nervous system, are permeable to cations and have an important role in physiological processes such as learning, memory, and synaptic development. The receptor is a tetramer of different subunits (typically heterodimer of subunit 1 with one or more of subunits 2A-D), forming a channel that is permeable to calcium, potassium, and sodium, and whose properties are determined by subunit composition. Alterations in the subunit composition of the receptor are associated with pathophysiological conditions such as Parkinson's disease, Alzheimer's disease, depression, and schizophrenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

GRIN2C links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 17-74854994-G-A is Benign according to our data. Variant chr17-74854994-G-A is described in ClinVar as [Benign]. Clinvar id is 769223.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.419 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRIN2C	NM_000835.6 linkuse as main transcript	c.99C>T	p.Ala33=	synonymous_variant	2/13	ENST00000293190.10	NP_000826.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRIN2C	ENST00000293190.10 linkuse as main transcript	c.99C>T	p.Ala33=	synonymous_variant	2/13	1	NM_000835.6	ENSP00000293190	P1

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

20988

AN:

152044

Hom.:

1782

Cov.:

show subpopulations

Gnomad AFR

AF:

0.179

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.127

Gnomad EAS

AF:

0.245

Gnomad SAS

AF:

0.248

Gnomad FIN

AF:

0.0708

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.0927

Gnomad OTH

AF:

0.163

GnomAD4 exome

AF:

0.109

AC:

158687

AN:

1455184

Hom.:

10701

Cov.:

AF XY:

0.113

AC XY:

81609

AN XY:

724190

show subpopulations

Gnomad4 AFR exome

AF:

0.182

Gnomad4 AMR exome

AF:

0.203

Gnomad4 ASJ exome

AF:

0.122

Gnomad4 EAS exome

AF:

0.251

Gnomad4 SAS exome

AF:

0.230

Gnomad4 FIN exome

AF:

0.0708

Gnomad4 NFE exome

AF:

0.0878

Gnomad4 OTH exome

AF:

0.138

GnomAD4 genome

AF:

0.138

AC:

21022

AN:

152162

Hom.:

1791

Cov.:

AF XY:

0.141

AC XY:

10476

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.179

Gnomad4 AMR

AF:

0.206

Gnomad4 ASJ

AF:

0.127

Gnomad4 EAS

AF:

0.246

Gnomad4 SAS

AF:

0.250

Gnomad4 FIN

AF:

0.0708

Gnomad4 NFE

AF:

0.0927

Gnomad4 OTH

AF:

0.163

Alfa

AF:

0.110

Hom.:

1728

Bravo

AF:

0.147

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

Labcorp Genetics (formerly Invitae), Labcorp

Feb 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

5.5

Splicing

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