NM_001256613.2:c.332C>T

Variant names:

• chr3-184104234-C-T
• rs760935074
• NM_001256613.2:c.332C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001256613.2(HTR3E):​c.332C>T​(p.Thr111Met) 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 1,612,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: HTR3E NM_001256613.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.64
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1593934).

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.332C>T	p.Thr111Met	missense	Exon 4 of 9	NP_001243542.1	A5X5Y0-1
	HTR3E	NM_001256614.1		c.332C>T	p.Thr111Met	missense	Exon 2 of 7	NP_001243543.1	A5X5Y0-6
	HTR3E	NM_182589.2		c.377C>T	p.Thr126Met	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.332C>T	p.Thr111Met	missense	Exon 4 of 9	ENSP00000401444.2	A5X5Y0-1
	HTR3E	ENST00000440596.2	TSL:1	c.332C>T	p.Thr111Met	missense	Exon 2 of 7	ENSP00000406050.2	A5X5Y0-6
	HTR3E	ENST00000335304.6	TSL:1	c.377C>T	p.Thr126Met	missense	Exon 3 of 8	ENSP00000335511.2	A5X5Y0-3

Frequencies

GnomAD3 genomes AF: 0.0000527 AC: 8 AN: 151866 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000968

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250344 AF XY: 0.0000148

Gnomad AFR exome AF: 0.0000620

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1460950 Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 6 AN XY: 726808

African (AFR) AF: 0.00 AC: 0 AN: 33398

American (AMR) AF: 0.00 AC: 0 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39624

South Asian (SAS) AF: 0.00 AC: 0 AN: 86150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1111580

Other (OTH) AF: 0.0000166 AC: 1 AN: 60324

GnomAD4 genome AF: 0.0000527 AC: 8 AN: 151866 Hom.: 0 Cov.: 30 AF XY: 0.0000405 AC XY: 3 AN XY: 74140

African (AFR) AF: 0.0000968 AC: 4 AN: 41308

American (AMR) AF: 0.0000656 AC: 1 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10538

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000178 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000546

EpiControl AF: 0.00

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	Benign	0.088
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.45
DANN	Benign	0.84
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-2.6
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.20
Sift	Benign	0.059	T
Sift4G	Benign	0.10	T
Polyphen		0.30	B
Vest4		0.071
MVP		0.57
MPC		0.075
ClinPred		0.12	T
GERP RS		-4.9
Varity_R		0.012
gMVP		0.074
Mutation Taster		=99/1	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: rs760935074; hg19: chr3-183822022;