11-113979273-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000869.6(HTR3A):āc.260G>Cā(p.Arg87Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000521 in 1,611,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 0.000056 ( 0 hom. )
Consequence
HTR3A
NM_000869.6 missense
NM_000869.6 missense
Scores
9
9
1
Clinical Significance
Conservation
PhyloP100: 6.63
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.93
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HTR3A | NM_000869.6 | c.260G>C | p.Arg87Pro | missense_variant | 3/9 | ENST00000504030.7 | NP_000860.3 | |
HTR3A | NM_213621.4 | c.260G>C | p.Arg87Pro | missense_variant | 3/8 | NP_998786.3 | ||
HTR3A | NM_001161772.3 | c.215G>C | p.Arg72Pro | missense_variant | 3/9 | NP_001155244.1 | ||
HTR3A | NR_046363.2 | n.478G>C | non_coding_transcript_exon_variant | 3/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HTR3A | ENST00000504030.7 | c.260G>C | p.Arg87Pro | missense_variant | 3/9 | 1 | NM_000869.6 | ENSP00000424189.2 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152050Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000121 AC: 3AN: 247988Hom.: 0 AF XY: 0.00000744 AC XY: 1AN XY: 134356
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GnomAD4 exome AF: 0.0000562 AC: 82AN: 1459122Hom.: 0 Cov.: 31 AF XY: 0.0000496 AC XY: 36AN XY: 726088
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GnomAD4 genome AF: 0.0000132 AC: 2AN: 152050Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74274
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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 04, 2022 | The c.278G>C (p.R93P) alteration is located in exon 3 (coding exon 3) of the HTR3A gene. This alteration results from a G to C substitution at nucleotide position 278, causing the arginine (R) at amino acid position 93 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;.;.;M;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;T
Vest4
MutPred
0.76
.;Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;.;
MVP
MPC
0.53
ClinPred
D
GERP RS
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at