rs56109847

Positions:

• chr3-184106769-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001256613.2(HTR3E):​c.*76G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.039 in 1,423,154 control chromosomes in the GnomAD database, including 1,254 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 0.028 (84 hom., cov: 32)
  • Exomes 𝑓: 0.040 (1170 hom.)
• Consequence: HTR3E NM_001256613.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0283 (4309/152178) while in subpopulation NFE AF= 0.0448 (3045/67994). AF 95% confidence interval is 0.0435. There are 84 homozygotes in gnomad4. There are 2007 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 84 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR3E	NM_001256613.2	c.*76G>A		3_prime_UTR_variant	9/9	ENST00000415389.6	NP_001243542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR3E	ENST00000415389.6	c.*76G>A		3_prime_UTR_variant	9/9	1	NM_001256613.2	ENSP00000401444.2
HTR3E	ENST00000335304.6	c.*76G>A		3_prime_UTR_variant	8/8	1		ENSP00000335511.2

Frequencies

GnomAD3 genomes AF: 0.0284 AC: 4312 AN: 152060 Hom.: 84 Cov.: 32

Gnomad AFR AF: 0.00843

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0195

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0131

Gnomad FIN AF: 0.0344

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0448

Gnomad OTH AF: 0.0335

GnomAD4 exome AF: 0.0402 AC: 51145 AN: 1270976 Hom.: 1170 Cov.: 19 AF XY: 0.0397 AC XY: 25336 AN XY: 637704

Gnomad4 AFR exome AF: 0.00690

Gnomad4 AMR exome AF: 0.0129

Gnomad4 ASJ exome AF: 0.0117

Gnomad4 EAS exome AF: 0.0000258

Gnomad4 SAS exome AF: 0.0179

Gnomad4 FIN exome AF: 0.0353

Gnomad4 NFE exome AF: 0.0474

Gnomad4 OTH exome AF: 0.0321

GnomAD4 genome AF: 0.0283 AC: 4309 AN: 152178 Hom.: 84 Cov.: 32 AF XY: 0.0270 AC XY: 2007 AN XY: 74376

Gnomad4 AFR AF: 0.00840

Gnomad4 AMR AF: 0.0194

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0129

Gnomad4 FIN AF: 0.0344

Gnomad4 NFE AF: 0.0448

Gnomad4 OTH AF: 0.0326

Alfa AF: 0.0337 Hom.: 16

Bravo AF: 0.0257

Asia WGS AF: 0.00606 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.10
DANN	Benign	0.37

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: rs56109847; hg19: chr3-183824557;