chr10-90748969-G-C

Variant names:

• chr10-90748969-G-C
• rs750208564
• NM_019859.4:c.1165C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_019859.4(HTR7):​c.1165C>G​(p.Arg389Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: HTR7 NM_019859.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.50

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.84

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR7	NM_019859.4	c.1165C>G	p.Arg389Gly	missense_variant	Exon 2 of 4	ENST00000336152.8	NP_062873.1
HTR7	NM_000872.5	c.1165C>G	p.Arg389Gly	missense_variant	Exon 2 of 3		NP_000863.1
HTR7	NM_019860.4	c.1165C>G	p.Arg389Gly	missense_variant	Exon 2 of 3		NP_062874.1
HTR7	XM_024447973.2	c.571C>G	p.Arg191Gly	missense_variant	Exon 2 of 4		XP_024303741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR7	ENST00000336152.8	c.1165C>G	p.Arg389Gly	missense_variant	Exon 2 of 4	1	NM_019859.4	ENSP00000337949.3
HTR7	ENST00000277874.10	c.1165C>G	p.Arg389Gly	missense_variant	Exon 2 of 3	1		ENSP00000277874.6
HTR7	ENST00000371719.2	c.1165C>G	p.Arg389Gly	missense_variant	Exon 2 of 3	1		ENSP00000360784.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152128 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152128 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74296

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	T;.;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.97	L;L;L
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-5.3	D;D;D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.0070	D;D;D
Polyphen		0.99	D;D;.
Vest4		0.93
MutPred		0.55		Loss of MoRF binding (P = 0.0314);Loss of MoRF binding (P = 0.0314);Loss of MoRF binding (P = 0.0314);
MVP		0.83
MPC		1.4
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.74
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

LitVar

Other links and lift over

dbSNP: rs750208564; hg19: chr10-92508726;