Variant 11-3666546-G-C 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.914C>G(p.Thr305Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,400,972 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: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CHRNA10
NM_020402.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.52

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=0.27207693).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA10	NM_020402.4 linkuse as main transcript	c.914C>G	p.Thr305Ser	missense_variant	5/5	ENST00000250699.2	NP_065135.2	Q9GZZ6
CHRNA10	NM_001303034.2 linkuse as main transcript	c.296C>G	p.Thr99Ser	missense_variant	5/5		NP_001289963.1	Q9GZZ6
CHRNA10	NM_001303035.2 linkuse as main transcript	c.296C>G	p.Thr99Ser	missense_variant	5/5		NP_001289964.1	Q9GZZ6C4IXS7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CHRNA10	ENST00000250699.2 linkuse as main transcript	c.914C>G	p.Thr305Ser	missense_variant	5/5	1	NM_020402.4	ENSP00000250699.2	Q9GZZ6
CHRNA10	ENST00000534359.1 linkuse as main transcript	c.367C>G	p.Leu123Val	missense_variant	5/5	1		ENSP00000437107.1	E9PNX2
CHRNA10	ENST00000526599.1 linkuse as main transcript	n.*685C>G		non_coding_transcript_exon_variant	5/5	1		ENSP00000432757.1	E9PNT7
CHRNA10	ENST00000526599.1 linkuse as main transcript	n.*685C>G		3_prime_UTR_variant	5/5	1		ENSP00000432757.1	E9PNT7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000490

AC:

AN:

204280

Hom.:

AF XY:

0.00

AC XY:

AN XY:

108648

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000209

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1400972

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

689412

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:

9.26e-7

Gnomad4 OTH exome

AF:

0.0000173

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

Jan 30, 2024

The c.914C>G (p.T305S) alteration is located in exon 5 (coding exon 5) of the CHRNA10 gene. This alteration results from a C to G substitution at nucleotide position 914, causing the threonine (T) at amino acid position 305 to be replaced by a serine (S). 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

0.31

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

DANN

Benign

0.97

Eigen

Uncertain

0.64

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.031

MetaRNN

Benign

0.27

MetaSVM

Uncertain

-0.21

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.26

Vest4

0.13

MutPred

0.24

Loss of glycosylation at P122 (P = 0.0902);

MVP

0.89

ClinPred

0.77

GERP RS

5.5

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