11-3666250-T-G

Position:

• chr11-3666250-T-G

Variant summary

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

The NM_020402.4(CHRNA10):​c.1210A>C​(p.Asn404His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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)
• Consequence: CHRNA10 NM_020402.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.13

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=0.25367147).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA10	NM_020402.4	c.1210A>C	p.Asn404His	missense_variant	5/5	ENST00000250699.2	NP_065135.2
CHRNA10	NM_001303034.2	c.592A>C	p.Asn198His	missense_variant	5/5		NP_001289963.1
CHRNA10	NM_001303035.2	c.592A>C	p.Asn198His	missense_variant	5/5		NP_001289964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA10	ENST00000250699.2	c.1210A>C	p.Asn404His	missense_variant	5/5	1	NM_020402.4	ENSP00000250699.2
CHRNA10	ENST00000534359	c.*291A>C		3_prime_UTR_variant	5/5	1		ENSP00000437107.1
CHRNA10	ENST00000526599.1	n.*981A>C		non_coding_transcript_exon_variant	5/5	1		ENSP00000432757.1
CHRNA10	ENST00000526599.1	n.*981A>C		3_prime_UTR_variant	5/5	1		ENSP00000432757.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2024

The c.1210A>C (p.N404H) alteration is located in exon 5 (coding exon 5) of the CHRNA10 gene. This alteration results from a A to C substitution at nucleotide position 1210, causing the asparagine (N) at amino acid position 404 to be replaced by a histidine (H). 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	0.086
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T
Eigen	Benign	-0.095
Eigen_PC	Benign	-0.073
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.69	N
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.11
Sift	Benign	0.040	D
Sift4G	Benign	0.092	T
Polyphen		0.74	P
Vest4		0.15
MutPred		0.38		Gain of disorder (P = 0.0683);
MVP		0.76
MPC		0.33
ClinPred		0.62	D
GERP RS		1.7
Varity_R		0.12
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr11-3687480;