rs7627615

Positions:

• chr3-184100628-G-A
• chr3-184100628-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001256613.2(HTR3E):​c.211G>A​(p.Ala71Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 1,613,590 control chromosomes in the GnomAD database, including 308,536 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.68 (36625 hom., cov: 30)
  • Exomes 𝑓: 0.61 (271911 hom.)
• Consequence: HTR3E NM_001256613.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.49

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.6547994E-7).
• BP6: Variant 3-184100628-G-A is Benign according to our data. Variant chr3-184100628-G-A is described in ClinVar as [Benign]. Clinvar id is 1242214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR3E	NM_001256613.2	c.211G>A	p.Ala71Thr	missense_variant	2/9	ENST00000415389.6	NP_001243542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR3E	ENST00000415389.6	c.211G>A	p.Ala71Thr	missense_variant	2/9	1	NM_001256613.2	ENSP00000401444.2

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103533 AN: 151720 Hom.: 36580 Cov.: 30

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.677

GnomAD3 exomes AF: 0.640 AC: 160765 AN: 251206 Hom.: 52593 AF XY: 0.631 AC XY: 85671 AN XY: 135798

Gnomad AFR exome AF: 0.882

Gnomad AMR exome AF: 0.715

Gnomad ASJ exome AF: 0.617

Gnomad EAS exome AF: 0.768

Gnomad SAS exome AF: 0.612

Gnomad FIN exome AF: 0.539

Gnomad NFE exome AF: 0.591

Gnomad OTH exome AF: 0.638

GnomAD4 exome AF: 0.606 AC: 886498 AN: 1461752 Hom.: 271911 Cov.: 54 AF XY: 0.605 AC XY: 439852 AN XY: 727196

Gnomad4 AFR exome AF: 0.892

Gnomad4 AMR exome AF: 0.707

Gnomad4 ASJ exome AF: 0.615

Gnomad4 EAS exome AF: 0.758

Gnomad4 SAS exome AF: 0.606

Gnomad4 FIN exome AF: 0.544

Gnomad4 NFE exome AF: 0.590

Gnomad4 OTH exome AF: 0.632

GnomAD4 genome AF: 0.683 AC: 103632 AN: 151838 Hom.: 36625 Cov.: 30 AF XY: 0.680 AC XY: 50404 AN XY: 74174

Gnomad4 AFR AF: 0.878

Gnomad4 AMR AF: 0.674

Gnomad4 ASJ AF: 0.604

Gnomad4 EAS AF: 0.763

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.680

Alfa AF: 0.614 Hom.: 74944

Bravo AF: 0.706

TwinsUK AF: 0.592 AC: 2196

ALSPAC AF: 0.606 AC: 2337

ESP6500AA AF: 0.871 AC: 3837

ESP6500EA AF: 0.588 AC: 5058

ExAC AF: 0.640 AC: 77751

Asia WGS AF: 0.732 AC: 2545 AN: 3478

EpiCase AF: 0.603

EpiControl AF: 0.610

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 18, 2020	This variant is associated with the following publications: (PMID: 23928294) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.1
DANN	Benign	0.87
DEOGEN2	Benign	0.042	T;.;.;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.046	T;T;T;T;T
MetaRNN	Benign	6.7e-7	T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.2	N;N;.;.;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	2.9	N;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	1.0	T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0	B;B;B;B;.
Vest4		0.061
MPC		0.055
ClinPred		0.0027	T
GERP RS		2.6
Varity_R		0.023
gMVP		0.030

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7627615; hg19: chr3-183818416; COSMIC: COSV58947508;