chr5-148523291-G-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000870.7(HTR4):c.409C>A(p.Arg137Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,890 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 (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
HTR4
NM_000870.7 missense
NM_000870.7 missense
Scores
5
8
5
Clinical Significance
Conservation
PhyloP100: 4.24
Genes affected
HTR4 (HGNC:5299): (5-hydroxytryptamine receptor 4) This gene is a member of the family of serotonin receptors, which are G protein coupled receptors that stimulate cAMP production in response to serotonin (5-hydroxytryptamine). The gene product is a glycosylated transmembrane protein that functions in both the peripheral and central nervous system to modulate the release of various neurotransmitters. Multiple transcript variants encoding proteins with distinct C-terminal sequences have been described. [provided by RefSeq, May 2010]
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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, 0.924
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HTR4 | NM_000870.7 | c.409C>A | p.Arg137Ser | missense_variant | 5/7 | ENST00000377888.8 | |
LOC107986462 | XR_001742935.2 | n.442-26794G>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HTR4 | ENST00000377888.8 | c.409C>A | p.Arg137Ser | missense_variant | 5/7 | 1 | NM_000870.7 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460890Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726746
GnomAD4 exome
AF:
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2
AN:
1460890
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Cov.:
31
AF XY:
AC XY:
0
AN XY:
726746
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
Bravo
AF:
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 | Sep 29, 2023 | The c.409C>A (p.R137S) alteration is located in exon 4 (coding exon 4) of the HTR4 gene. This alteration results from a C to A substitution at nucleotide position 409, causing the arginine (R) at amino acid position 137 to be replaced by a serine (S). 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
Uncertain
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;.;.;D;D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;M;M;M;M;M
MutationTaster
Benign
D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D;D;D;.
REVEL
Uncertain
Sift
Benign
D;D;D;T;D;T;D;.
Sift4G
Benign
T;T;T;T;T;T;T;T
Polyphen
D;.;D;.;D;.;.;D
Vest4
MutPred
Gain of ubiquitination at K132 (P = 0.1181);Gain of ubiquitination at K132 (P = 0.1181);Gain of ubiquitination at K132 (P = 0.1181);Gain of ubiquitination at K132 (P = 0.1181);Gain of ubiquitination at K132 (P = 0.1181);Gain of ubiquitination at K132 (P = 0.1181);Gain of ubiquitination at K132 (P = 0.1181);Gain of ubiquitination at K132 (P = 0.1181);
MVP
MPC
0.36
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at