chr10-90857666-C-T

Variant summary

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

The NM_019859.4(HTR7):​c.6G>A​(p.Met2Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000176 in 1,568,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

HTR7
NM_019859.4 missense

Scores

3
3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.752
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]

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=0.41333482).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HTR7NM_019859.4 linkuse as main transcriptc.6G>A p.Met2Ile missense_variant 1/4 ENST00000336152.8
HTR7NM_000872.5 linkuse as main transcriptc.6G>A p.Met2Ile missense_variant 1/3
HTR7NM_019860.4 linkuse as main transcriptc.6G>A p.Met2Ile missense_variant 1/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HTR7ENST00000336152.8 linkuse as main transcriptc.6G>A p.Met2Ile missense_variant 1/41 NM_019859.4 P34969-1
HTR7ENST00000277874.10 linkuse as main transcriptc.6G>A p.Met2Ile missense_variant 1/31 A1P34969-2
HTR7ENST00000371719.2 linkuse as main transcriptc.6G>A p.Met2Ile missense_variant 1/31 P4P34969-3

Frequencies

GnomAD3 genomes
AF:
0.0000855
AC:
13
AN:
152106
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000128
AC:
22
AN:
172176
Hom.:
0
AF XY:
0.000134
AC XY:
13
AN XY:
96698
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000638
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000415
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000207
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000186
AC:
263
AN:
1416106
Hom.:
0
Cov.:
32
AF XY:
0.000175
AC XY:
123
AN XY:
702682
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000322
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000862
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000210
Gnomad4 OTH exome
AF:
0.000222
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152212
Hom.:
0
Cov.:
32
AF XY:
0.0000941
AC XY:
7
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000216
Hom.:
0
Bravo
AF:
0.000102
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.000115
AC:
13

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 submitterclinical testingAmbry GeneticsMar 01, 2023The c.6G>A (p.M2I) 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 6, causing the methionine (M) at amino acid position 2 to be replaced by an isoleucine (I). 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
Uncertain
0.51
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.14
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.12
T;.;.
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.19
FATHMM_MKL
Benign
0.64
D
LIST_S2
Benign
0.72
T;T;T
M_CAP
Pathogenic
0.88
D
MetaRNN
Benign
0.41
T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.69
N;N;N
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-0.080
N;N;N
REVEL
Benign
0.29
Sift
Pathogenic
0.0
D;D;D
Sift4G
Uncertain
0.054
T;T;T
Polyphen
0.26
B;B;.
Vest4
0.41
MutPred
0.23
Loss of disorder (P = 0.071);Loss of disorder (P = 0.071);Loss of disorder (P = 0.071);
MVP
0.84
MPC
0.46
ClinPred
0.12
T
GERP RS
2.9
Varity_R
0.82
gMVP
0.51

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.

Other links and lift over

dbSNP: rs201619956; hg19: chr10-92617423; API