3-184060222-G-C

Position:

• chr3-184060222-G-C

Variant summary

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

The NM_130770.3(HTR3C):​c.1214G>C​(p.Gly405Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 1,613,744 control chromosomes in the GnomAD database, including 230,186 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.52 (21006 hom., cov: 31)
  • Exomes 𝑓: 0.53 (209180 hom.)
• Consequence: HTR3C NM_130770.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673

Genes affected

HTR3C (HGNC:24003): (5-hydroxytryptamine receptor 3C) The product of this gene belongs to the ligand-gated ion channel receptor superfamily. This gene encodes subunit C of the type 3 receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor causes fast, depolarizing responses in neurons after activation. Genes encoding subunits C, D and E form a cluster on chromosome 3. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.6808539E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR3C	NM_130770.3	c.1214G>C	p.Gly405Ala	missense_variant	9/9	ENST00000318351.2	NP_570126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR3C	ENST00000318351.2	c.1214G>C	p.Gly405Ala	missense_variant	9/9	1	NM_130770.3	ENSP00000322617.1

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79169 AN: 151770 Hom.: 20996 Cov.: 31

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.531

GnomAD3 exomes AF: 0.555 AC: 139475 AN: 251306 Hom.: 39851 AF XY: 0.547 AC XY: 74322 AN XY: 135818

Gnomad AFR exome AF: 0.465

Gnomad AMR exome AF: 0.687

Gnomad ASJ exome AF: 0.614

Gnomad EAS exome AF: 0.730

Gnomad SAS exome AF: 0.473

Gnomad FIN exome AF: 0.526

Gnomad NFE exome AF: 0.521

Gnomad OTH exome AF: 0.559

GnomAD4 exome AF: 0.532 AC: 777777 AN: 1461856 Hom.: 209180 Cov.: 74 AF XY: 0.529 AC XY: 384724 AN XY: 727228

Gnomad4 AFR exome AF: 0.471

Gnomad4 AMR exome AF: 0.677

Gnomad4 ASJ exome AF: 0.609

Gnomad4 EAS exome AF: 0.729

Gnomad4 SAS exome AF: 0.470

Gnomad4 FIN exome AF: 0.527

Gnomad4 NFE exome AF: 0.523

Gnomad4 OTH exome AF: 0.550

GnomAD4 genome AF: 0.521 AC: 79204 AN: 151888 Hom.: 21006 Cov.: 31 AF XY: 0.523 AC XY: 38839 AN XY: 74200

Gnomad4 AFR AF: 0.463

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.723

Gnomad4 SAS AF: 0.468

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.536

Alfa AF: 0.497 Hom.: 5355

Bravo AF: 0.532

TwinsUK AF: 0.522 AC: 1935

ALSPAC AF: 0.525 AC: 2024

ESP6500AA AF: 0.472 AC: 2079

ESP6500EA AF: 0.531 AC: 4568

ExAC AF: 0.544 AC: 66049

Asia WGS AF: 0.630 AC: 2188 AN: 3478

EpiCase AF: 0.539

EpiControl AF: 0.544

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.023
DANN	Benign	0.13
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.73	T
MetaRNN	Benign	0.0000027	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.18
Sift	Benign	0.67	T
Sift4G	Benign	0.80	T
Polyphen		0.65	P
Vest4		0.023
MPC		0.046
ClinPred		0.016	T
GERP RS		-6.8
Varity_R		0.030
gMVP		0.098

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: rs6807362; hg19: chr3-183778010; COSMIC: COSV59174604;