NM_019859.4:c.130T>A

Variant names:

• chr10-90857542-A-T
• rs1206667530
• NM_019859.4:c.130T>A

Variant summary

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

The NM_019859.4(HTR7):​c.130T>A​(p.Trp44Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HTR7 NM_019859.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.37

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR7	NM_019859.4	c.130T>A	p.Trp44Arg	missense_variant	Exon 1 of 4	ENST00000336152.8	NP_062873.1
HTR7	NM_000872.5	c.130T>A	p.Trp44Arg	missense_variant	Exon 1 of 3		NP_000863.1
HTR7	NM_019860.4	c.130T>A	p.Trp44Arg	missense_variant	Exon 1 of 3		NP_062874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR7	ENST00000336152.8	c.130T>A	p.Trp44Arg	missense_variant	Exon 1 of 4	1	NM_019859.4	ENSP00000337949.3
HTR7	ENST00000277874.10	c.130T>A	p.Trp44Arg	missense_variant	Exon 1 of 3	1		ENSP00000277874.6
HTR7	ENST00000371719.2	c.130T>A	p.Trp44Arg	missense_variant	Exon 1 of 3	1		ENSP00000360784.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.26	T;.;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.35	T;T;T
M_CAP	Pathogenic	0.80	D
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.69	N;N;N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.0	N;N;N
REVEL	Benign	0.096
Sift	Benign	0.12	T;T;T
Sift4G	Benign	0.26	T;T;T
Polyphen		0.015	B;P;.
Vest4		0.62
MutPred		0.41		Gain of disorder (P = 0.0059);Gain of disorder (P = 0.0059);Gain of disorder (P = 0.0059);
MVP		0.85
MPC		0.77
ClinPred		0.38	T
GERP RS		2.7
Varity_R		0.16
gMVP		0.72

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

Other links and lift over

dbSNP: rs1206667530; hg19: chr10-92617299;