Variant 1-224684821-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152495.2(CNIH3):c.176G>A(p.Arg59His) variant causes a missense change. The variant allele was found at a frequency of 0.0000483 in 1,613,942 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

CNIH3
NM_152495.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.46

Variant links:

Genes affected

CNIH3 (HGNC:26802): (cornichon family AMPA receptor auxiliary protein 3) Predicted to enable channel regulator activity. Involved in regulation of AMPA receptor activity. Predicted to be located in dendritic shaft and postsynaptic membrane. Predicted to be part of AMPA glutamate receptor complex. Predicted to be active in dendrite and glutamatergic synapse. [provided by Alliance of Genome Resources, Apr 2022]

CNIH3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNIH3	NM_152495.2 linkuse as main transcript	c.176G>A	p.Arg59His	missense_variant	3/6	ENST00000272133.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CNIH3	ENST00000272133.4 linkuse as main transcript	c.176G>A	p.Arg59His	missense_variant	3/6	1	NM_152495.2	P1
CNIH3	ENST00000478120.5 linkuse as main transcript	n.497G>A		non_coding_transcript_exon_variant	5/8	5
CNIH3	ENST00000481095.5 linkuse as main transcript	n.468G>A		non_coding_transcript_exon_variant	5/7	3
CNIH3	ENST00000498382.5 linkuse as main transcript	n.325G>A		non_coding_transcript_exon_variant	3/6	2

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000637

AC:

AN:

251374

Hom.:

AF XY:

0.0000736

AC XY:

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000704

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000472

AC:

AN:

1461772

Hom.:

Cov.:

AF XY:

0.0000509

AC XY:

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.0000405

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000901

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 05, 2023

The c.176G>A (p.R59H) alteration is located in exon 3 (coding exon 3) of the CNIH3 gene. This alteration results from a G to A substitution at nucleotide position 176, causing the arginine (R) at amino acid position 59 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.060

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.70

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.4

REVEL

Benign

0.27

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.019

Polyphen

1.0

Vest4

0.76

MutPred

0.62

Loss of MoRF binding (P = 0.0255);

MVP

0.54

MPC

1.1

ClinPred

0.36

GERP RS

4.5

Varity_R

0.43

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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