11-113982977-G-C

Variant names:

• chr11-113982977-G-C
• rs3737457
• NM_000869.6:c.375-143G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000869.6(HTR3A):​c.375-143G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000132 in 760,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 33)
  • Exomes 𝑓: 0.0000013 (0 hom.)
• Consequence: HTR3A NM_000869.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.893
• Publications: 0 publications found

Genes affected

HTR3A (HGNC:5297): (5-hydroxytryptamine receptor 3A) The product of this gene belongs to the ligand-gated ion channel receptor superfamily. This gene encodes subunit A 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. It appears that the heteromeric combination of A and B subunits is necessary to provide the full functional features of this receptor, since either subunit alone results in receptors with very low conductance and response amplitude. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000869.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3A	NM_000869.6	MANE Select	c.375-143G>C		intron	N/A	NP_000860.3	P46098-1
	HTR3A	NM_213621.4		c.375-143G>C		intron	N/A	NP_998786.3	P46098-2
	HTR3A	NM_001161772.3		c.330-143G>C		intron	N/A	NP_001155244.1	P46098-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3A	ENST00000504030.7	TSL:1 MANE Select	c.375-143G>C		intron	N/A	ENSP00000424189.2	P46098-1
	HTR3A	ENST00000375498.6	TSL:1	c.393-143G>C		intron	N/A	ENSP00000364648.2	P46098-4
	HTR3A	ENST00000355556.6	TSL:2	c.393-143G>C		intron	N/A	ENSP00000347754.2	P46098-5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000132 AC: 1 AN: 760358 Hom.: 0 AF XY: 0.00000251 AC XY: 1 AN XY: 397812

African (AFR) AF: 0.00 AC: 0 AN: 19458

American (AMR) AF: 0.00 AC: 0 AN: 35014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20052

East Asian (EAS) AF: 0.00 AC: 0 AN: 33704

South Asian (SAS) AF: 0.00 AC: 0 AN: 65356

European-Finnish (FIN) AF: 0.0000256 AC: 1 AN: 39084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3846

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 506688

Other (OTH) AF: 0.00 AC: 0 AN: 37156

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.48
PhyloP100		-0.89

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

Other links and lift over

dbSNP: rs3737457; hg19: chr11-113853699;