Variant 10-90857475-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_019859.4(HTR7):c.197A>G(p.Asn66Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000082 ( 0 hom. )

Consequence

HTR7
NM_019859.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.02

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 2 ACMG points.

PM1

In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity 5HT7R_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17478874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
HTR7	NM_019859.4 linkuse as main transcript	c.197A>G	p.Asn66Ser	missense_variant	1/4	ENST00000336152.8	NP_062873.1
HTR7	NM_000872.5 linkuse as main transcript	c.197A>G	p.Asn66Ser	missense_variant	1/3		NP_000863.1
HTR7	NM_019860.4 linkuse as main transcript	c.197A>G	p.Asn66Ser	missense_variant	1/3		NP_062874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR7	ENST00000336152.8 linkuse as main transcript	c.197A>G	p.Asn66Ser	missense_variant	1/4	1	NM_019859.4	ENSP00000337949		P34969-1
HTR7	ENST00000277874.10 linkuse as main transcript	c.197A>G	p.Asn66Ser	missense_variant	1/3	1		ENSP00000277874	A1	P34969-2
HTR7	ENST00000371719.2 linkuse as main transcript	c.197A>G	p.Asn66Ser	missense_variant	1/3	1		ENSP00000360784	P4	P34969-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247322

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134438

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

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:

0.00000821

AC:

AN:

1461420

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727014

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

Apr 20, 2023

The c.197A>G (p.N66S) alteration is located in exon 1 (coding exon 1) of the HTR7 gene. This alteration results from a A to G substitution at nucleotide position 197, causing the asparagine (N) at amino acid position 66 to be replaced by a serine (S). 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

0.086

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.14

T;.;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.76

T;T;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.3

L;L;L

MutationTaster

Benign

0.89

D;D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.092

Sift

Benign

0.096

T;T;T

Sift4G

Uncertain

0.034

D;D;D

Polyphen

0.010

B;B;.

Vest4

0.30

MutPred

0.33

Gain of glycosylation at N66 (P = 0.0012);Gain of glycosylation at N66 (P = 0.0012);Gain of glycosylation at N66 (P = 0.0012);

MVP

0.76

MPC

0.33

ClinPred

0.25

GERP RS

2.8

Varity_R

0.21

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