1-224617190-G-T

Variant names:

• chr1-224617190-G-T
• rs369518337
• NM_152495.2:c.16G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152495.2(CNIH3):​c.16G>T​(p.Ala6Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,782 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A6T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CNIH3 NM_152495.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.21
• Publications: 0 publications found

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-AS2 (HGNC:41162): (CNIH3 antisense RNA 2)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38802937).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152495.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNIH3	NM_152495.2	MANE Select	c.16G>T	p.Ala6Ser	missense	Exon 1 of 6	NP_689708.1	Q8TBE1
	CNIH3	NM_001322305.2		c.16G>T	p.Ala6Ser	missense	Exon 1 of 5	NP_001309234.1
	CNIH3	NM_001322302.2		c.166-63768G>T		intron	N/A	NP_001309231.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNIH3	ENST00000272133.4	TSL:1 MANE Select	c.16G>T	p.Ala6Ser	missense	Exon 1 of 6	ENSP00000272133.3	Q8TBE1
	CNIH3	ENST00000860910.1		c.16G>T	p.Ala6Ser	missense	Exon 1 of 5	ENSP00000530969.1
	CNIH3	ENST00000933029.1		c.16G>T	p.Ala6Ser	missense	Exon 1 of 4	ENSP00000603088.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251044 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461782 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727192

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111966

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.046	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.7	L
PhyloP100		7.2
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.22
Sift	Benign	0.082	T
Sift4G	Benign	0.20	T
Polyphen		1.0	D
Vest4		0.41
MutPred		0.64		Gain of glycosylation at A6 (P = 0.0156)
MVP		0.21
MPC		0.61
ClinPred		0.90	D
GERP RS		3.9
Varity_R		0.21
gMVP		0.82
Mutation Taster		=54/46	polymorphism

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

Other links and lift over

dbSNP: rs369518337; hg19: chr1-224804892;