10-90743643-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_019859.4(HTR7):​c.1343C>A​(p.Pro448Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: not found (cov: 32)

Consequence

HTR7
NM_019859.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.12
Variant links:
Genes affected
HTR7 (HGNC:5302): (5-hydroxytryptamine receptor 7) The neurotransmitter, serotonin, is thought to play a role in various cognitive and behavioral functions. The serotonin receptor encoded by this gene belongs to the superfamily of G protein-coupled receptors and the gene is a candidate locus for involvement in autistic disorder and other neuropsychiatric disorders. Three splice variants have been identified which encode proteins that differ in the length of their carboxy terminal ends. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04314643).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HTR7NM_019859.4 linkc.1343C>A p.Pro448Gln missense_variant Exon 3 of 4 ENST00000336152.8 NP_062873.1 P34969-1
HTR7XM_024447973.2 linkc.749C>A p.Pro250Gln missense_variant Exon 3 of 4 XP_024303741.1
HTR7NM_000872.5 linkc.1296-1115C>A intron_variant Intron 2 of 2 NP_000863.1 P34969-2
HTR7NM_019860.4 linkc.*2-1115C>A intron_variant Intron 2 of 2 NP_062874.1 P34969-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HTR7ENST00000336152.8 linkc.1343C>A p.Pro448Gln missense_variant Exon 3 of 4 1 NM_019859.4 ENSP00000337949.3 P34969-1
HTR7ENST00000277874.10 linkc.1296-1115C>A intron_variant Intron 2 of 2 1 ENSP00000277874.6 P34969-2
HTR7ENST00000371719.2 linkc.*2-1115C>A intron_variant Intron 2 of 2 1 ENSP00000360784.2 P34969-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.088
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
0.053
DANN
Benign
0.40
DEOGEN2
Benign
0.14
T
Eigen
Benign
-2.2
Eigen_PC
Benign
-2.2
FATHMM_MKL
Benign
0.0015
N
LIST_S2
Benign
0.18
T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.043
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-0.14
N
REVEL
Benign
0.053
Sift
Benign
0.79
T
Sift4G
Pathogenic
0.0
D
Polyphen
0.0
B
Vest4
0.15
MutPred
0.086
Loss of catalytic residue at P447 (P = 0.016);
MVP
0.45
MPC
0.38
ClinPred
0.022
T
GERP RS
-3.8
Varity_R
0.027
gMVP
0.12

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.16
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: rs33954285; hg19: chr10-92503400; API