rs62625041

chr11-113975301-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_000869.6(HTR3A):c.-25C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,612,804 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00079 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (2 hom.)
• Consequence: HTR3A NM_000869.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.496

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

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 11-113975301-C-T is Benign according to our data. Variant chr11-113975301-C-T is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR3A	NM_000869.6	c.-25C>T		5_prime_UTR_variant	1/9	ENST00000504030.7
HTR3A	NM_213621.4	c.-25C>T		5_prime_UTR_variant	1/8
HTR3A	NR_046363.2	n.194C>T		non_coding_transcript_exon_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR3A	ENST00000504030.7	c.-25C>T		5_prime_UTR_variant	1/9	1	NM_000869.6	P1

Frequencies

GnomAD3 genomes AF: 0.000795 AC: 121 AN: 152228 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00156

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000818 AC: 204 AN: 249390 Hom.: 0 AF XY: 0.000816 AC XY: 110 AN XY: 134884

Gnomad AFR exome AF: 0.000495

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000289

Gnomad NFE exome AF: 0.00164

Gnomad OTH exome AF: 0.000656

GnomAD4 exome AF: 0.00140 AC: 2041 AN: 1460458 Hom.: 2 Cov.: 33 AF XY: 0.00134 AC XY: 972 AN XY: 726504

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.0000671

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000552

Gnomad4 NFE exome AF: 0.00176

Gnomad4 OTH exome AF: 0.000679

GnomAD4 genome AF: 0.000794 AC: 121 AN: 152346 Hom.: 0 Cov.: 33 AF XY: 0.000604 AC XY: 45 AN XY: 74496

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00156

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00118 Hom.: 1

Bravo AF: 0.000714

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000981

EpiControl AF: 0.00166

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	8.1
Dann	Benign	0.91

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs62625041; hg19: chr11-113846023;