11-113981322-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000869.6(HTR3A):c.374+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 1,551,966 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (6 hom.)
• Consequence: HTR3A NM_000869.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.450

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-113981322-G-A is Benign according to our data. Variant chr11-113981322-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 714264.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-113981322-G-A is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR3A	NM_000869.6	c.374+10G>A		intron_variant		ENST00000504030.7
HTR3A	NM_001161772.3	c.329+10G>A		intron_variant
HTR3A	NM_213621.4	c.374+10G>A		intron_variant
HTR3A	NR_046363.2	n.592+10G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR3A	ENST00000504030.7	c.374+10G>A		intron_variant		1	NM_000869.6	P1

Frequencies

GnomAD3 genomes AF: 0.00127 AC: 194 AN: 152168 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00210

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00119 AC: 299 AN: 251280 Hom.: 2 AF XY: 0.00137 AC XY: 186 AN XY: 135804

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000492

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00209

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00180

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.00178 AC: 2486 AN: 1399680 Hom.: 6 Cov.: 23 AF XY: 0.00181 AC XY: 1270 AN XY: 699900

Gnomad4 AFR exome AF: 0.0000621

Gnomad4 AMR exome AF: 0.000762

Gnomad4 ASJ exome AF: 0.000737

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.00171

Gnomad4 FIN exome AF: 0.0000749

Gnomad4 NFE exome AF: 0.00206

Gnomad4 OTH exome AF: 0.00177

GnomAD4 genome AF: 0.00127 AC: 194 AN: 152286 Hom.: 1 Cov.: 32 AF XY: 0.00105 AC XY: 78 AN XY: 74464

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00210

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00169 Hom.: 0

Bravo AF: 0.00145

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 18, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.70
Dann	Benign	0.52

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: rs369511862; hg19: chr11-113852044;