chr3-184054731-C-A

Variant names:

• chr3-184054731-C-A
• rs143289420
• NM_130770.3:c.78C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_130770.3(HTR3C):​c.78C>A​(p.Asp26Glu) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D26G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HTR3C NM_130770.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.525

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06701887).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR3C	NM_130770.3	c.78C>A	p.Asp26Glu	missense_variant	Exon 2 of 9	ENST00000318351.2	NP_570126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR3C	ENST00000318351.2	c.78C>A	p.Asp26Glu	missense_variant	Exon 2 of 9	1	NM_130770.3	ENSP00000322617.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1444244 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 717774

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	1.1
DANN	Benign	0.92
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.074	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.14
Sift	Benign	0.27	T
Sift4G	Benign	0.50	T
Polyphen		0.42	B
Vest4		0.13
MutPred		0.46		Loss of sheet (P = 0.0315);
MVP		0.15
MPC		0.041
ClinPred		0.16	T
GERP RS		0.000080
Varity_R		0.042
gMVP		0.018

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs143289420; hg19: chr3-183772519;