3-184100470-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001256614.1(HTR3E):​c.98C>T​(p.Ser33Leu) 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 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S33W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HTR3E
NM_001256614.1 missense

Scores

2
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.63
Variant links:
Genes affected
HTR3E (HGNC:24005): (5-hydroxytryptamine receptor 3E) This locus encodes a 5-hydroxytryptamine (serotonin) receptor subunit. The encoded protein, subunit E, may play a role in neurotransmission in myenteric neurons. Genes encoding subunits C, D and E form a cluster on chromosome 3. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Feb 2012]
HTR3E-AS1 (HGNC:41032): (HTR3E antisense RNA 1)

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ACMG classification

Classification made for transcript

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=0.0911361).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HTR3ENM_001256613.2 linkc.68-15C>T intron_variant Intron 1 of 8 ENST00000415389.6 NP_001243542.1 A5X5Y0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HTR3EENST00000415389.6 linkc.68-15C>T intron_variant Intron 1 of 8 1 NM_001256613.2 ENSP00000401444.2 A5X5Y0-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251488
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461884
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727240
show subpopulations
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.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
0.45
DANN
Benign
0.85
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.0054
N
LIST_S2
Benign
0.41
T;T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.091
T;T;T
MetaSVM
Benign
-0.68
T
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.98
N;N;N
REVEL
Benign
0.17
Sift
Uncertain
0.0070
D;D;D
Sift4G
Uncertain
0.011
D;D;D
Polyphen
0.88
P;B;.
Vest4
0.066
MutPred
0.41
Loss of catalytic residue at S33 (P = 0.0055);Loss of catalytic residue at S33 (P = 0.0055);Loss of catalytic residue at S33 (P = 0.0055);
MVP
0.30
MPC
0.052
ClinPred
0.083
T
GERP RS
-1.6
gMVP
0.072

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs202036764; hg19: chr3-183818258; COSMIC: COSV58949485; API