chr3-184100632-T-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001256613.2(HTR3E):​c.215T>A​(p.Met72Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,613,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. M72T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

HTR3E
NM_001256613.2 missense

Scores

1
8
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.04
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.969

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HTR3ENM_001256613.2 linkc.215T>A p.Met72Lys missense_variant Exon 2 of 9 ENST00000415389.6 NP_001243542.1 A5X5Y0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HTR3EENST00000415389.6 linkc.215T>A p.Met72Lys missense_variant Exon 2 of 9 1 NM_001256613.2 ENSP00000401444.2 A5X5Y0-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152106
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000966
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251102
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135768
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461770
Hom.:
0
Cov.:
36
AF XY:
0.00000275
AC XY:
2
AN XY:
727194
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152106
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.0000966
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.54
BayesDel_addAF
Uncertain
0.023
T
BayesDel_noAF
Uncertain
-0.020
CADD
Benign
19
DANN
Benign
0.97
DEOGEN2
Benign
0.40
T;.;.;.;.;.
Eigen
Benign
0.061
Eigen_PC
Benign
0.091
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.57
T;T;T;D;T;T
M_CAP
Benign
0.055
D
MetaRNN
Pathogenic
0.97
D;D;D;D;D;D
MetaSVM
Benign
-0.39
T
MutationAssessor
Benign
1.4
L;L;.;.;.;.
PrimateAI
Benign
0.35
T
PROVEAN
Uncertain
-3.4
D;D;D;D;D;D
REVEL
Uncertain
0.62
Sift
Uncertain
0.0020
D;D;D;D;D;D
Sift4G
Uncertain
0.0020
D;D;D;D;D;D
Polyphen
0.63
P;P;P;.;P;.
Vest4
0.58
MutPred
0.75
Loss of stability (P = 0.012);Loss of stability (P = 0.012);.;.;.;.;
MVP
0.84
MPC
0.15
ClinPred
0.92
D
GERP RS
3.8
Varity_R
0.74
gMVP
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs201948885; hg19: chr3-183818420; API