NM_000869.6:c.568T>C

Variant names:

• chr11-113986038-T-C
• NM_000869.6:c.568T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000869.6(HTR3A):​c.568T>C​(p.Trp190Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HTR3A NM_000869.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.17
• Publications: 0 publications found

Genes affected

HTR3A (HGNC:5297): (5-hydroxytryptamine receptor 3A) The product of this gene belongs to the ligand-gated ion channel receptor superfamily. This gene encodes subunit A of the type 3 receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor causes fast, depolarizing responses in neurons after activation. It appears that the heteromeric combination of A and B subunits is necessary to provide the full functional features of this receptor, since either subunit alone results in receptors with very low conductance and response amplitude. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4123943).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000869.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3A	NM_000869.6	MANE Select	c.568T>C	p.Trp190Arg	missense	Exon 6 of 9	NP_000860.3	P46098-1
	HTR3A	NM_213621.4		c.568T>C	p.Trp190Arg	missense	Exon 6 of 8	NP_998786.3	P46098-2
	HTR3A	NM_001161772.3		c.523T>C	p.Trp175Arg	missense	Exon 6 of 9	NP_001155244.1	P46098-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3A	ENST00000504030.7	TSL:1 MANE Select	c.568T>C	p.Trp190Arg	missense	Exon 6 of 9	ENSP00000424189.2	P46098-1
	HTR3A	ENST00000375498.6	TSL:1	c.586T>C	p.Trp196Arg	missense	Exon 6 of 9	ENSP00000364648.2	P46098-4
	HTR3A	ENST00000355556.6	TSL:2	c.586T>C	p.Trp196Arg	missense	Exon 6 of 8	ENSP00000347754.2	P46098-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	0.97
DEOGEN2	Uncertain	0.42	T
Eigen	Benign	0.084
Eigen_PC	Benign	0.083
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.2
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.39
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.10	T
Vest4		0.61
MutPred		0.39		Gain of disorder (P = 0.0091)
MVP		0.52
MPC		0.53
ClinPred		0.78	D
GERP RS		1.4
Varity_R		0.15
gMVP		0.69
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr11-113856760;