10-90857261-G-T

Position:

• chr10-90857261-G-T

Variant summary

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

The NM_019859.4(HTR7):​c.411C>A​(p.Phe137Leu) 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. 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: 0.370

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=0.36606175).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR7	NM_019859.4	c.411C>A	p.Phe137Leu	missense_variant	1/4	ENST00000336152.8
HTR7	NM_000872.5	c.411C>A	p.Phe137Leu	missense_variant	1/3
HTR7	NM_019860.4	c.411C>A	p.Phe137Leu	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR7	ENST00000336152.8	c.411C>A	p.Phe137Leu	missense_variant	1/4	1	NM_019859.4
HTR7	ENST00000277874.10	c.411C>A	p.Phe137Leu	missense_variant	1/3	1		A1
HTR7	ENST00000371719.2	c.411C>A	p.Phe137Leu	missense_variant	1/3	1		P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Aug 16, 2021

The c.411C>A (p.F137L) alteration is located in exon 1 (coding exon 1) of the HTR7 gene. This alteration results from a C to A substitution at nucleotide position 411, causing the phenylalanine (F) at amino acid position 137 to be replaced by a leucine (L). 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	0.99
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.15	T;.;.
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.79	T;T;T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.22	N;N;N
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.69	N;N;N
REVEL	Uncertain	0.37
Sift	Benign	0.42	T;T;T
Sift4G	Benign	0.76	T;T;T
Polyphen		0.67	P;B;.
Vest4		0.56
MutPred		0.61		Loss of catalytic residue at F137 (P = 0.0061);Loss of catalytic residue at F137 (P = 0.0061);Loss of catalytic residue at F137 (P = 0.0061);
MVP		0.84
MPC		1.0
ClinPred		0.46	T
GERP RS		1.1
Varity_R		0.35
gMVP		0.82

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: chr10-92617018;