Variant 10-90857479-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_019859.4(HTR7):c.193G>A(p.Asp65Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,288 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: 6.8e-7 ( 0 hom. )

Consequence

HTR7
NM_019859.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.93

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 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=0.27148497).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HTR7	NM_019859.4 linkuse as main transcript	c.193G>A	p.Asp65Asn	missense_variant	1/4	ENST00000336152.8
HTR7	NM_000872.5 linkuse as main transcript	c.193G>A	p.Asp65Asn	missense_variant	1/3
HTR7	NM_019860.4 linkuse as main transcript	c.193G>A	p.Asp65Asn	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR7	ENST00000336152.8 linkuse as main transcript	c.193G>A	p.Asp65Asn	missense_variant	1/4	1	NM_019859.4		P34969-1
HTR7	ENST00000277874.10 linkuse as main transcript	c.193G>A	p.Asp65Asn	missense_variant	1/3	1		A1	P34969-2
HTR7	ENST00000371719.2 linkuse as main transcript	c.193G>A	p.Asp65Asn	missense_variant	1/3	1		P4	P34969-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461288

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726940

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jul 20, 2021

The c.193G>A (p.D65N) alteration is located in exon 1 (coding exon 1) of the HTR7 gene. This alteration results from a G to A substitution at nucleotide position 193, causing the aspartic acid (D) at amino acid position 65 to be replaced by an asparagine (N). 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

0.074

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;.;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.091

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.83

T;T;T

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.7

L;L;L

MutationTaster

Benign

0.69

D;D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

0.12

N;N;N

REVEL

Benign

0.10

Sift

Benign

0.13

T;T;T

Sift4G

Benign

0.16

T;T;T

Polyphen

0.15

B;B;.

Vest4

0.17

MutPred

0.27

Gain of glycosylation at P63 (P = 0.0941);Gain of glycosylation at P63 (P = 0.0941);Gain of glycosylation at P63 (P = 0.0941);

MVP

0.75

MPC

0.40

ClinPred

0.77

GERP RS

4.0

Varity_R

0.14

gMVP

0.28

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over