chr11-113983153-C-T

Variant names:

• chr11-113983153-C-T
• rs150595107
• NM_000869.6:c.408C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_000869.6(HTR3A):​c.408C>T​(p.Tyr136Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000212 in 1,614,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00061 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: HTR3A NM_000869.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.249
• Publications: 1 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 11-113983153-C-T is Benign according to our data. Variant chr11-113983153-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2642383.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.249 with no splicing effect.

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.408C>T	p.Tyr136Tyr	synonymous	Exon 5 of 9	NP_000860.3	P46098-1
	HTR3A	NM_213621.4		c.408C>T	p.Tyr136Tyr	synonymous	Exon 5 of 8	NP_998786.3	P46098-2
	HTR3A	NM_001161772.3		c.363C>T	p.Tyr121Tyr	synonymous	Exon 5 of 9	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.408C>T	p.Tyr136Tyr	synonymous	Exon 5 of 9	ENSP00000424189.2	P46098-1
	HTR3A	ENST00000375498.6	TSL:1	c.426C>T	p.Tyr142Tyr	synonymous	Exon 5 of 9	ENSP00000364648.2	P46098-4
	HTR3A	ENST00000355556.6	TSL:2	c.426C>T	p.Tyr142Tyr	synonymous	Exon 5 of 8	ENSP00000347754.2	P46098-5

Frequencies

GnomAD3 genomes AF: 0.000604 AC: 92 AN: 152216 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000203 AC: 51 AN: 251488 AF XY: 0.000118

Gnomad AFR exome AF: 0.00234

Gnomad AMR exome AF: 0.000173

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000527

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000170 AC: 249 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.000158 AC XY: 115 AN XY: 727242

African (AFR) AF: 0.00236 AC: 79 AN: 33480

American (AMR) AF: 0.000112 AC: 5 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.000127 AC: 141 AN: 1112002

Other (OTH) AF: 0.000298 AC: 18 AN: 60396

GnomAD4 genome AF: 0.000611 AC: 93 AN: 152334 Hom.: 0 Cov.: 33 AF XY: 0.000631 AC XY: 47 AN XY: 74498

African (AFR) AF: 0.00200 AC: 83 AN: 41588

American (AMR) AF: 0.000196 AC: 3 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000112 Hom.: 0

Bravo AF: 0.000593

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.5
DANN	Benign	0.43
PhyloP100		-0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs150595107; hg19: chr11-113853875; COSMIC: COSV55468193;