Variant 11-3667351-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020402.4(CHRNA10):c.776A>T(p.His259Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000483 in 1,448,538 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CHRNA10
NM_020402.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.03

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4208855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CHRNA10	NM_020402.4 linkuse as main transcript	c.776A>T	p.His259Leu	missense_variant	4/5	ENST00000250699.2
CHRNA10	NM_001303034.2 linkuse as main transcript	c.158A>T	p.His53Leu	missense_variant	4/5
CHRNA10	NM_001303035.2 linkuse as main transcript	c.158A>T	p.His53Leu	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CHRNA10	ENST00000250699.2 linkuse as main transcript	c.776A>T	p.His259Leu	missense_variant	4/5	1	NM_020402.4	P1
CHRNA10	ENST00000534359.1 linkuse as main transcript	c.229A>T	p.Thr77Ser	missense_variant	4/5	1
CHRNA10	ENST00000526599.1 linkuse as main transcript	c.*547A>T		3_prime_UTR_variant, NMD_transcript_variant	4/5	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000483

AC:

AN:

1448538

Hom.:

Cov.:

AF XY:

0.00000693

AC XY:

AN XY:

721040

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 08, 2022

The c.776A>T (p.H259L) alteration is located in exon 4 (coding exon 4) of the CHRNA10 gene. This alteration results from a A to T substitution at nucleotide position 776, causing the histidine (H) at amino acid position 259 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

0.095

BayesDel_addAF

Uncertain

0.073

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Benign

0.90

DEOGEN2

Uncertain

0.47

Eigen

Benign

0.066

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.74

M_CAP

Benign

0.037

MetaRNN

Benign

0.42

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.27

MutationTaster

Benign

0.99

D;N

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.33

Sift

Benign

0.91

Sift4G

Benign

0.22

Polyphen

0.0010

Vest4

0.45

MutPred

0.56

Loss of disorder (P = 0.0588);

MVP

0.89

MPC

0.16

ClinPred

0.72

GERP RS

4.0

Varity_R

0.35

gMVP

0.49

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