rs374967830

Variant names:

• chr3-184104270-C-A
• rs374967830
• NM_001256613.2:c.368C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-184104270-C-A
• chr3-184104270-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001256613.2(HTR3E):​c.368C>A​(p.Pro123Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,612,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: HTR3E NM_001256613.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.44
• Publications: 2 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: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.907

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.368C>A	p.Pro123Gln	missense	Exon 4 of 9	NP_001243542.1	A5X5Y0-1
	HTR3E	NM_001256614.1		c.368C>A	p.Pro123Gln	missense	Exon 2 of 7	NP_001243543.1	A5X5Y0-6
	HTR3E	NM_182589.2		c.413C>A	p.Pro138Gln	missense	Exon 3 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.368C>A	p.Pro123Gln	missense	Exon 4 of 9	ENSP00000401444.2	A5X5Y0-1
	HTR3E	ENST00000440596.2	TSL:1	c.368C>A	p.Pro123Gln	missense	Exon 2 of 7	ENSP00000406050.2	A5X5Y0-6
	HTR3E	ENST00000335304.6	TSL:1	c.413C>A	p.Pro138Gln	missense	Exon 3 of 8	ENSP00000335511.2	A5X5Y0-3

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152000 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000362 AC: 9 AN: 248630 AF XY: 0.0000447

Gnomad AFR exome AF: 0.000437

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000891

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000959 AC: 14 AN: 1460266 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 726344

African (AFR) AF: 0.000359 AC: 12 AN: 33414

American (AMR) AF: 0.0000224 AC: 1 AN: 44604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39620

South Asian (SAS) AF: 0.00 AC: 0 AN: 85942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111246

Other (OTH) AF: 0.0000166 AC: 1 AN: 60320

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152000 Hom.: 0 Cov.: 30 AF XY: 0.0000808 AC XY: 6 AN XY: 74232

African (AFR) AF: 0.000290 AC: 12 AN: 41366

American (AMR) AF: 0.00 AC: 0 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000205 Hom.: 0

Bravo AF: 0.0000907

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000659 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.47
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.71	D
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.079	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	3.9	H
PhyloP100		2.4
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Pathogenic	0.77
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.78
MVP		0.90
MPC		0.34
ClinPred		0.99	D
GERP RS		2.6
Varity_R		0.70
gMVP		0.36
Mutation Taster		=91/9	polymorphism

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: rs374967830; hg19: chr3-183822058;