Genetic Variant HTR7:p.Leu454Val (chr10-90743626-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_019859.4(HTR7):c.1360C>G(p.Leu454Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

HTR7
NM_019859.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.174

Publications

0 publications found

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]

HTR7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06347275).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019859.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HTR7	NM_019859.4	MANE Select	c.1360C>G	p.Leu454Val	missense	Exon 3 of 4	NP_062873.1	P34969-1
HTR7	NM_000872.5		c.1296-1098C>G		intron	N/A	NP_000863.1	P34969-2
HTR7	NM_019860.4		c.*2-1098C>G		intron	N/A	NP_062874.1	P34969-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HTR7	ENST00000336152.8	TSL:1 MANE Select	c.1360C>G	p.Leu454Val	missense	Exon 3 of 4	ENSP00000337949.3	P34969-1
HTR7	ENST00000277874.10	TSL:1	c.1296-1098C>G		intron	N/A	ENSP00000277874.6	P34969-2
HTR7	ENST00000371719.2	TSL:1	c.*2-1098C>G		intron	N/A	ENSP00000360784.2	P34969-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251416

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461684

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727154

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.0000224

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.000101

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111844

Other (OTH)

AF:

0.0000166

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.50

CADD

Benign

1.3

(source)

DANN

Benign

0.38

DEOGEN2

Benign

0.094

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.33

M_CAP

Benign

0.020

MetaRNN

Benign

0.063

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.17

PrimateAI

Benign

0.29

PROVEAN

Benign

0.030

REVEL

Benign

0.10

Sift

Pathogenic

0.0

Sift4G

Benign

0.51

Polyphen

0.17

Vest4

0.18

MutPred

0.18

Gain of MoRF binding (P = 0.1899)

MVP

0.35

MPC

0.42

ClinPred

0.049

GERP RS

-3.0

Varity_R

0.15

gMVP

0.077

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over