11-3666450-C-T

Variant names:

• chr11-3666450-C-T
• NM_020402.4:c.1010G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020402.4(CHRNA10):​c.1010G>A​(p.Arg337Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CHRNA10 NM_020402.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.568

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.092945814).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA10	NM_020402.4	c.1010G>A	p.Arg337Lys	missense_variant	Exon 5 of 5	ENST00000250699.2	NP_065135.2
CHRNA10	NM_001303034.2	c.392G>A	p.Arg131Lys	missense_variant	Exon 5 of 5		NP_001289963.1
CHRNA10	NM_001303035.2	c.392G>A	p.Arg131Lys	missense_variant	Exon 5 of 5		NP_001289964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA10	ENST00000250699.2	c.1010G>A	p.Arg337Lys	missense_variant	Exon 5 of 5	1	NM_020402.4	ENSP00000250699.2
CHRNA10	ENST00000534359	c.*91G>A		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000437107.1
CHRNA10	ENST00000526599.1	n.*781G>A		non_coding_transcript_exon_variant	Exon 5 of 5	1		ENSP00000432757.1
CHRNA10	ENST00000526599.1	n.*781G>A		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000432757.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461448 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727002

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1010G>A (p.R337K) alteration is located in exon 5 (coding exon 5) of the CHRNA10 gene. This alteration results from a G to A substitution at nucleotide position 1010, causing the arginine (R) at amino acid position 337 to be replaced by a lysine (K). 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	0.15
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Benign	0.85
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.94	L
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.070
Sift	Benign	0.40	T
Sift4G	Benign	0.61	T
Polyphen		0.072	B
Vest4		0.068
MutPred		0.67		Gain of ubiquitination at R337 (P = 0.0247);
MVP		0.36
MPC		0.14
ClinPred		0.26	T
GERP RS		2.3
Varity_R		0.11
gMVP		0.73

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-3687680;