Variant 11-3667504-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_020402.4(CHRNA10):c.623C>T(p.Pro208Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000168 in 1,581,078 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

CHRNA10
NM_020402.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.81

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:

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
CHRNA10	NM_020402.4 linkuse as main transcript	c.623C>T	p.Pro208Leu	missense_variant	4/5	ENST00000250699.2
CHRNA10	NM_001303034.2 linkuse as main transcript	c.5C>T	p.Pro2Leu	missense_variant	4/5
CHRNA10	NM_001303035.2 linkuse as main transcript	c.5C>T	p.Pro2Leu	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CHRNA10	ENST00000250699.2 linkuse as main transcript	c.623C>T	p.Pro208Leu	missense_variant	4/5	1	NM_020402.4	P1
CHRNA10	ENST00000534359.1 linkuse as main transcript	c.76C>T	p.Arg26Trp	missense_variant	4/5	1
CHRNA10	ENST00000526599.1 linkuse as main transcript	c.*394C>T		3_prime_UTR_variant, NMD_transcript_variant	4/5	1

Frequencies

GnomAD3 genomes

AF:

0.0000790

AC:

AN:

151992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000104

AC:

AN:

201952

Hom.:

AF XY:

0.000123

AC XY:

AN XY:

113566

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000162

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000619

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000165

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000177

AC:

253

AN:

1428970

Hom.:

Cov.:

AF XY:

0.000165

AC XY:

117

AN XY:

710624

show subpopulations

Gnomad4 AFR exome

AF:

0.0000315

Gnomad4 AMR exome

AF:

0.0000958

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000220

Gnomad4 OTH exome

AF:

0.0000676

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000176

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000688

AC:

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

Nov 14, 2023

The c.623C>T (p.P208L) alteration is located in exon 4 (coding exon 4) of the CHRNA10 gene. This alteration results from a C to T substitution at nucleotide position 623, causing the proline (P) at amino acid position 208 to be replaced by a leucine (L). 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

0.28

BayesDel_addAF

Uncertain

0.061

BayesDel_noAF

Uncertain

0.11

Cadd

Pathogenic

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.52

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.46

MetaRNN

Uncertain

0.71

MetaSVM

Uncertain

-0.0088

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

D;N

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-9.9

REVEL

Pathogenic

0.68

Sift

Uncertain

0.011

Sift4G

Uncertain

0.025

Polyphen

1.0

Vest4

0.58

MVP

0.86

MPC

0.44

ClinPred

0.98

GERP RS

5.2

Varity_R

0.42

gMVP

0.65

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