3-184104798-A-G

Position:

• chr3-184104798-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001256613.2(HTR3E):​c.401A>G​(p.Asp134Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: HTR3E NM_001256613.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.14

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15273353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR3E	NM_001256613.2	c.401A>G	p.Asp134Gly	missense_variant	5/9	ENST00000415389.6	NP_001243542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR3E	ENST00000415389.6	c.401A>G	p.Asp134Gly	missense_variant	5/9	1	NM_001256613.2	ENSP00000401444.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.446A>G (p.D149G) alteration is located in exon 4 (coding exon 4) of the HTR3E gene. This alteration results from a A to G substitution at nucleotide position 446, causing the aspartic acid (D) at amino acid position 149 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	19
DANN	Benign	0.73
DEOGEN2	Benign	0.11	T;.;.;.;.;.
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.62	T;T;T;T;T;T
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.15	T;T;T;T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.1	M;.;.;.;M;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.6	N;N;N;N;N;N
REVEL	Benign	0.25
Sift	Benign	0.87	T;T;T;T;T;T
Sift4G	Benign	0.69	T;T;T;T;T;T
Polyphen		0.28	B;B;P;.;P;.
Vest4		0.096
MutPred		0.49		Gain of glycosylation at T136 (P = 0.0195);.;.;.;Gain of glycosylation at T136 (P = 0.0195);.;
MVP		0.54
MPC		0.28
ClinPred		0.13	T
GERP RS		2.6
Varity_R		0.051
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1712315426; hg19: chr3-183822586;