10-90743610-T-C

Position:

• chr10-90743610-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019859.4(HTR7):​c.1376A>G​(p.His459Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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)
• Consequence: HTR7 NM_019859.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.687

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]

ACMG classification

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=0.08265403).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR7	NM_019859.4	c.1376A>G	p.His459Arg	missense_variant	3/4	ENST00000336152.8
HTR7	XM_024447973.2	c.782A>G	p.His261Arg	missense_variant	3/4
HTR7	NM_000872.5	c.1296-1082A>G		intron_variant
HTR7	NM_019860.4	c.*2-1082A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR7	ENST00000336152.8	c.1376A>G	p.His459Arg	missense_variant	3/4	1	NM_019859.4
HTR7	ENST00000277874.10	c.1296-1082A>G		intron_variant		1		A1
HTR7	ENST00000371719.2	c.*2-1082A>G		intron_variant		1		P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 06, 2023

The c.1376A>G (p.H459R) alteration is located in exon 3 (coding exon 3) of the HTR7 gene. This alteration results from a A to G substitution at nucleotide position 1376, causing the histidine (H) at amino acid position 459 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	Benign	0.069
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	4.5
DANN	Benign	0.80
DEOGEN2	Benign	0.092	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.081
Sift	Benign	0.37	T
Sift4G	Benign	0.60	T
Polyphen		0.46	P
Vest4		0.24
MutPred		0.30		Gain of MoRF binding (P = 0.0199);
MVP		0.55
MPC		0.51
ClinPred		0.17	T
GERP RS		1.3
Varity_R		0.032
gMVP		0.075

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr10-92503367;