6-77462368-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000863.3(HTR1B):ā€‹c.1036T>Cā€‹(p.Phe346Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000052 in 1,613,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.000051 ( 0 hom. )

Consequence

HTR1B
NM_000863.3 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.37
Variant links:
Genes affected
HTR1B (HGNC:5287): (5-hydroxytryptamine receptor 1B) The protein encoded by this intronless gene is a G-protein coupled receptor for serotonin (5-hydroxytryptamine). Ligand binding activates second messengers that inhibit the activity of adenylate cyclase and manage the release of serotonin, dopamine, and acetylcholine in the brain. The encoded protein may be involved in several neuropsychiatric disorders and therefore is often a target of antidepressant and other psychotherapeutic drugs. [provided by RefSeq, Nov 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.059317827).
BS2
High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HTR1BNM_000863.3 linkuse as main transcriptc.1036T>C p.Phe346Leu missense_variant 1/1 ENST00000369947.5
LOC105377864XM_047419660.1 linkuse as main transcriptc.-3742-12158A>G intron_variant
LOC105377864XM_047419659.1 linkuse as main transcriptc.-11856A>G 5_prime_UTR_variant 1/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HTR1BENST00000369947.5 linkuse as main transcriptc.1036T>C p.Phe346Leu missense_variant 1/1 NM_000863.3 P1

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152198
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
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:
0.000175
AC:
44
AN:
251490
Hom.:
0
AF XY:
0.000132
AC XY:
18
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00127
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000506
AC:
74
AN:
1461798
Hom.:
0
Cov.:
34
AF XY:
0.0000413
AC XY:
30
AN XY:
727198
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00159
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:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152198
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000589
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
Alfa
AF:
0.00000635
Hom.:
0
Bravo
AF:
0.000102
ExAC
AF:
0.000115
AC:
14

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 submitterclinical testingAmbry GeneticsOct 05, 2021The c.1036T>C (p.F346L) alteration is located in exon 1 (coding exon 1) of the HTR1B gene. This alteration results from a T to C substitution at nucleotide position 1036, causing the phenylalanine (F) at amino acid position 346 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.86
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Uncertain
-0.080
CADD
Benign
21
DANN
Benign
0.95
DEOGEN2
Benign
0.072
T
Eigen
Benign
-0.13
Eigen_PC
Benign
0.11
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.18
T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.059
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.10
N
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
0.11
N
REVEL
Benign
0.28
Sift
Benign
0.50
T
Sift4G
Benign
0.83
T
Polyphen
0.0020
B
Vest4
0.38
MutPred
0.57
Loss of ubiquitination at K341 (P = 0.1062);
MVP
0.90
MPC
0.75
ClinPred
0.091
T
GERP RS
5.3
Varity_R
0.38
gMVP
0.82

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: rs757401382; hg19: chr6-78172085; API