NM_000869.6:c.375-143G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000869.6(HTR3A):​c.375-143G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0448 in 912,376 control chromosomes in the GnomAD database, including 3,030 homozygotes. 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: 𝑓 0.071 (823 hom., cov: 33)
  • Exomes 𝑓: 0.039 (2207 hom.)
• Consequence: HTR3A NM_000869.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.893
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.0710 AC: 10803 AN: 152062 Hom.: 808 Cov.: 33

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.00990

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0121

Gnomad OTH AF: 0.0683

GnomAD4 exome AF: 0.0395 AC: 29996 AN: 760196 Hom.: 2207 AF XY: 0.0400 AC XY: 15914 AN XY: 397730

African (AFR) AF: 0.153 AC: 2965 AN: 19436

American (AMR) AF: 0.243 AC: 8509 AN: 34968

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 282 AN: 20048

East Asian (EAS) AF: 0.113 AC: 3822 AN: 33694

South Asian (SAS) AF: 0.0977 AC: 6380 AN: 65332

European-Finnish (FIN) AF: 0.0105 AC: 411 AN: 39084

Middle Eastern (MID) AF: 0.0338 AC: 130 AN: 3842

European-Non Finnish (NFE) AF: 0.0116 AC: 5878 AN: 506644

Other (OTH) AF: 0.0436 AC: 1619 AN: 37148

GnomAD4 genome AF: 0.0714 AC: 10872 AN: 152180 Hom.: 823 Cov.: 33 AF XY: 0.0724 AC XY: 5385 AN XY: 74404

African (AFR) AF: 0.149 AC: 6191 AN: 41516

American (AMR) AF: 0.154 AC: 2345 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3470

East Asian (EAS) AF: 0.123 AC: 636 AN: 5164

South Asian (SAS) AF: 0.116 AC: 561 AN: 4818

European-Finnish (FIN) AF: 0.00990 AC: 105 AN: 10608

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0122 AC: 827 AN: 68006

Other (OTH) AF: 0.0733 AC: 155 AN: 2116

Alfa AF: 0.0331 Hom.: 115

Bravo AF: 0.0862

Asia WGS AF: 0.146 AC: 507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.52
PhyloP100		-0.89
Mutation Taster		=100/0	polymorphism (auto)

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;