Variant 10-90857556-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_019859.4(HTR7):c.116C>A(p.Pro39Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000025 in 1,597,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P39R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

HTR7
NM_019859.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.732

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:

Genome browser will be placed here

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=0.13303116).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HTR7	NM_019859.4 linkuse as main transcript	c.116C>A	p.Pro39Gln	missense_variant	1/4	ENST00000336152.8
HTR7	NM_000872.5 linkuse as main transcript	c.116C>A	p.Pro39Gln	missense_variant	1/3
HTR7	NM_019860.4 linkuse as main transcript	c.116C>A	p.Pro39Gln	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR7	ENST00000336152.8 linkuse as main transcript	c.116C>A	p.Pro39Gln	missense_variant	1/4	1	NM_019859.4		P34969-1
HTR7	ENST00000277874.10 linkuse as main transcript	c.116C>A	p.Pro39Gln	missense_variant	1/3	1		A1	P34969-2
HTR7	ENST00000371719.2 linkuse as main transcript	c.116C>A	p.Pro39Gln	missense_variant	1/3	1		P4	P34969-3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000194

AC:

AN:

206270

Hom.:

AF XY:

0.0000175

AC XY:

AN XY:

114028

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:

0.0000461

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000263

AC:

AN:

1445340

Hom.:

Cov.:

AF XY:

0.0000279

AC XY:

AN XY:

717576

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:

0.0000199

Gnomad4 NFE exome

AF:

0.0000308

Gnomad4 OTH exome

AF:

0.0000503

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000344

AC:

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 submitter

clinical testing

Ambry Genetics

May 09, 2022

The c.116C>A (p.P39Q) alteration is located in exon 1 (coding exon 1) of the HTR7 gene. This alteration results from a C to A substitution at nucleotide position 116, causing the proline (P) at amino acid position 39 to be replaced by a glutamine (Q). 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

Benign

0.079

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.46

CADD

Benign

0.94

DANN

Benign

0.96

DEOGEN2

Benign

0.12

T;.;.

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.55

T;T;T

M_CAP

Pathogenic

0.44

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.22

N;N;N

REVEL

Benign

0.050

Sift

Uncertain

0.022

D;T;T

Sift4G

Benign

0.10

T;T;T

Polyphen

0.028

B;B;.

Vest4

0.21

MutPred

0.30

Loss of disorder (P = 0.0877);Loss of disorder (P = 0.0877);Loss of disorder (P = 0.0877);

MVP

0.74

MPC

0.54

ClinPred

0.068

GERP RS

-0.67

Varity_R

0.070

gMVP

0.46

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over