chr10-90748887-T-C

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_019859.4(HTR7):c.1247A>G(p.His416Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,614,072 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

HTR7
NM_019859.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38794303).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR7	NM_019859.4 link	c.1247A>G	p.His416Arg	missense_variant	Exon 2 of 4	ENST00000336152.8	NP_062873.1	P34969-1
HTR7	NM_000872.5 link	c.1247A>G	p.His416Arg	missense_variant	Exon 2 of 3		NP_000863.1	P34969-2
HTR7	NM_019860.4 link	c.1247A>G	p.His416Arg	missense_variant	Exon 2 of 3		NP_062874.1	P34969-3
HTR7	XM_024447973.2 link	c.653A>G	p.His218Arg	missense_variant	Exon 2 of 4		XP_024303741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HTR7	ENST00000336152.8 link	c.1247A>G	p.His416Arg	missense_variant	Exon 2 of 4	1	NM_019859.4	ENSP00000337949.3	P34969-1
HTR7	ENST00000277874.10 link	c.1247A>G	p.His416Arg	missense_variant	Exon 2 of 3	1		ENSP00000277874.6	P34969-2
HTR7	ENST00000371719.2 link	c.1247A>G	p.His416Arg	missense_variant	Exon 2 of 3	1		ENSP00000360784.2	P34969-3

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

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:

0.000108

AC:

AN:

251118

Hom.:

AF XY:

0.0000958

AC XY:

AN XY:

135698

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000781

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:

0.0000267

AC:

AN:

1461844

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000805

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000204

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00203

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

Bravo

AF:

0.000223

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1247A>G (p.H416R) alteration is located in exon 2 (coding exon 2) of the HTR7 gene. This alteration results from a A to G substitution at nucleotide position 1247, causing the histidine (H) at amino acid position 416 to be replaced by an arginine (R). 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

0.65

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;.;.

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Benign

0.034

MetaRNN

Benign

0.39

T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

0.97

L;L;L

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.21

Sift

Uncertain

0.022

D;D;T

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.96

D;D;.

Vest4

0.72

MutPred

0.35

Gain of MoRF binding (P = 0.0084);Gain of MoRF binding (P = 0.0084);Gain of MoRF binding (P = 0.0084);

MVP

0.92

MPC

0.78

ClinPred

0.20

GERP RS

5.6

Varity_R

0.22

gMVP

0.81

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