Variant 11-3667429-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_020402.4(CHRNA10):c.698G>A(p.Arg233His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000009 in 1,444,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

CHRNA10
NM_020402.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.34

Variant links:

Genes affected

CHRNA10 (HGNC:13800): (cholinergic receptor nicotinic alpha 10 subunit) Predicted to enable acetylcholine-gated cation-selective channel activity. Acts upstream of or within positive regulation of cytosolic calcium ion concentration. Predicted to be located in membrane. Predicted to be active in cholinergic synapse and neuron projection. Predicted to be integral component of postsynaptic specialization membrane. [provided by Alliance of Genome Resources, Apr 2022]

CHRNA10 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1402672).

BP6

Variant 11-3667429-C-T is Benign according to our data. Variant chr11-3667429-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3267152.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA10	NM_020402.4 linkuse as main transcript	c.698G>A	p.Arg233His	missense_variant	4/5	ENST00000250699.2	NP_065135.2	Q9GZZ6
CHRNA10	NM_001303034.2 linkuse as main transcript	c.80G>A	p.Arg27His	missense_variant	4/5		NP_001289963.1	Q9GZZ6
CHRNA10	NM_001303035.2 linkuse as main transcript	c.80G>A	p.Arg27His	missense_variant	4/5		NP_001289964.1	Q9GZZ6C4IXS7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CHRNA10	ENST00000250699.2 linkuse as main transcript	c.698G>A	p.Arg233His	missense_variant	4/5	1	NM_020402.4	ENSP00000250699.2	Q9GZZ6
CHRNA10	ENST00000534359.1 linkuse as main transcript	c.151G>A	p.Ala51Thr	missense_variant	4/5	1		ENSP00000437107.1	E9PNX2
CHRNA10	ENST00000526599.1 linkuse as main transcript	n.*469G>A		non_coding_transcript_exon_variant	4/5	1		ENSP00000432757.1	E9PNT7
CHRNA10	ENST00000526599.1 linkuse as main transcript	n.*469G>A		3_prime_UTR_variant	4/5	1		ENSP00000432757.1	E9PNT7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000452

AC:

AN:

221112

Hom.:

AF XY:

0.0000326

AC XY:

AN XY:

122596

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000297

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000900

AC:

AN:

1444280

Hom.:

Cov.:

AF XY:

0.00000557

AC XY:

AN XY:

718618

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000271

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:

0.0000167

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000168

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 14, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Benign

0.94

Eigen

Benign

0.13

Eigen_PC

Benign

0.062

FATHMM_MKL

Benign

0.59

M_CAP

Uncertain

0.092

MetaRNN

Benign

0.14

MetaSVM

Uncertain

-0.17

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.20

Sift4G

Benign

0.47

Vest4

0.23

MutPred

0.13

Gain of glycosylation at A51 (P = 0.0035);

MVP

0.70

ClinPred

0.50

GERP RS

3.2

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.

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