chr3-184036506-G-C

Position:

• chr3-184036506-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000382489.3(HTR3D):​c.511+1G>C variant causes a splice donor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 1,613,688 control chromosomes in the GnomAD database, including 169,278 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.50 (20231 hom., cov: 33)
  • Exomes 𝑓: 0.45 (149047 hom.)
• Consequence: HTR3D ENST00000382489.3 splice_donor
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.657

Genes affected

HTR3D (HGNC:24004): (5-hydroxytryptamine receptor 3D) The protein encoded this gene belongs to the ligand-gated ion channel receptor superfamily. This gene encodes subunit D of the type 3 receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a mitogen and a hormone. This hormone has been linked to neuropsychiatric disorders, including anxiety, depression, and migraine. Serotonin receptors causes fast and depolarizing responses in neurons following activation. The genes encoding subunits C, D and E of this type 3 receptor form a cluster on chromosome 3. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.461416).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR3D	NM_001145143.1	c.329G>C	p.Gly110Ala	missense_variant	4/8	ENST00000428798.7
HTR3D	NM_001163646.2	c.511+1G>C		splice_donor_variant
HTR3D	NM_182537.3	c.107G>C	p.Gly36Ala	missense_variant	3/6
HTR3D	NM_001410851.1	c.3+1284G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR3D	ENST00000382489.3	c.511+1G>C		splice_donor_variant		1		P1
HTR3D	ENST00000428798.7	c.329G>C	p.Gly110Ala	missense_variant	4/8	5	NM_001145143.1
HTR3D	ENST00000334128.6	c.107G>C	p.Gly36Ala	missense_variant	3/6	1
HTR3D	ENST00000453435.1	c.3+1284G>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76288 AN: 152040 Hom.: 20212 Cov.: 33

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.517

GnomAD3 exomes AF: 0.456 AC: 114642 AN: 251224 Hom.: 27001 AF XY: 0.452 AC XY: 61426 AN XY: 135776

Gnomad AFR exome AF: 0.671

Gnomad AMR exome AF: 0.434

Gnomad ASJ exome AF: 0.578

Gnomad EAS exome AF: 0.496

Gnomad SAS exome AF: 0.452

Gnomad FIN exome AF: 0.318

Gnomad NFE exome AF: 0.442

Gnomad OTH exome AF: 0.467

GnomAD4 exome AF: 0.448 AC: 654727 AN: 1461530 Hom.: 149047 Cov.: 59 AF XY: 0.448 AC XY: 325485 AN XY: 727062

Gnomad4 AFR exome AF: 0.678

Gnomad4 AMR exome AF: 0.437

Gnomad4 ASJ exome AF: 0.577

Gnomad4 EAS exome AF: 0.553

Gnomad4 SAS exome AF: 0.446

Gnomad4 FIN exome AF: 0.328

Gnomad4 NFE exome AF: 0.439

Gnomad4 OTH exome AF: 0.466

GnomAD4 genome AF: 0.502 AC: 76347 AN: 152158 Hom.: 20231 Cov.: 33 AF XY: 0.495 AC XY: 36807 AN XY: 74390

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.510

Alfa AF: 0.427 Hom.: 4212

Bravo AF: 0.520

TwinsUK AF: 0.422 AC: 1563

ALSPAC AF: 0.441 AC: 1701

ESP6500AA AF: 0.646 AC: 2848

ESP6500EA AF: 0.449 AC: 3862

ExAC AF: 0.462 AC: 56051

Asia WGS AF: 0.484 AC: 1687 AN: 3478

EpiCase AF: 0.465

EpiControl AF: 0.470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.5
DANN	Benign	0.95
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.018	N
MutationTaster	Benign	1.0	P;P;P;P
ClinPred		0.0099	T
GERP RS		4.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs6443930; hg19: chr3-183754294; COSMIC: COSV61913608;