10-90857479-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.93

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 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	UniProt
HTR7	NM_019859.4	c.193G>A	p.Asp65Asn	missense_variant	1/4	ENST00000336152.8
HTR7	NM_000872.5	c.193G>A	p.Asp65Asn	missense_variant	1/3
HTR7	NM_019860.4	c.193G>A	p.Asp65Asn	missense_variant	1/3

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461288 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726940

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.: 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

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	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.13	T;.;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.091
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.7	L;L;L
MutationTaster	Benign	0.69	D;D;D;D
PrimateAI	Uncertain	0.60	T
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	D
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.

Other links and lift over

hg19: chr10-92617236;