3-184105280-G-A

Variant names:

• chr3-184105280-G-A
• rs766257187
• NM_001256613.2:c.573G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001256613.2(HTR3E):​c.573G>A​(p.Leu191Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,206 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: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HTR3E NM_001256613.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202
• Publications: 0 publications found

Genes affected

HTR3E (HGNC:24005): (5-hydroxytryptamine receptor 3E) This locus encodes a 5-hydroxytryptamine (serotonin) receptor subunit. The encoded protein, subunit E, may play a role in neurotransmission in myenteric neurons. Genes encoding subunits C, D and E form a cluster on chromosome 3. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Feb 2012]

HTR3E-AS1 (HGNC:41032): (HTR3E antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=0.202 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256613.2. 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
	HTR3E	NM_001256613.2	MANE Select	c.573G>A	p.Leu191Leu	synonymous	Exon 6 of 9	NP_001243542.1	A5X5Y0-1
	HTR3E	NM_001256614.1		c.651G>A	p.Leu217Leu	synonymous	Exon 4 of 7	NP_001243543.1	A5X5Y0-6
	HTR3E	NM_182589.2		c.618G>A	p.Leu206Leu	synonymous	Exon 5 of 8	NP_872395.2	A5X5Y0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3E	ENST00000415389.6	TSL:1 MANE Select	c.573G>A	p.Leu191Leu	synonymous	Exon 6 of 9	ENSP00000401444.2	A5X5Y0-1
	HTR3E	ENST00000440596.2	TSL:1	c.651G>A	p.Leu217Leu	synonymous	Exon 4 of 7	ENSP00000406050.2	A5X5Y0-6
	HTR3E	ENST00000335304.6	TSL:1	c.618G>A	p.Leu206Leu	synonymous	Exon 5 of 8	ENSP00000335511.2	A5X5Y0-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460206 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726292

African (AFR) AF: 0.00 AC: 0 AN: 33424

American (AMR) AF: 0.00 AC: 0 AN: 44278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26048

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 85780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111498

Other (OTH) AF: 0.00 AC: 0 AN: 60336

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	4.5
DANN	Benign	0.78
PhyloP100		0.20

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: rs766257187; hg19: chr3-183823068;