dbSNP rs148962973: HTR3D:c.-80C>G (chr3-184035174-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_182537.3(HTR3D):c.-80C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,399,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

HTR3D
NM_182537.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.514

Publications

2 publications found

Variant links:

Genes affected

HTR3D (HGNC:24004): (5-hydroxytryptamine receptor 3D) The protein encoded this gene belongs to the ligand-gated ion channel receptor superfamily. This gene encodes subunit D of the type 3 receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a mitogen and a hormone. This hormone has been linked to neuropsychiatric disorders, including anxiety, depression, and migraine. Serotonin receptors causes fast and depolarizing responses in neurons following activation. The genes encoding subunits C, D and E of this type 3 receptor form a cluster on chromosome 3. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2009]

HTR3D links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3844417).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182537.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HTR3D	NM_001145143.1	MANE Select	c.67-4C>G	splice_region intron	N/A	NP_001138615.1	Q70Z44-4
HTR3D	NM_182537.3		c.-80C>G	5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	NP_872343.2
HTR3D	NM_001410851.1		c.-46C>G	5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	NP_001397780.1	Q70Z44-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HTR3D	ENST00000334128.6	TSL:1	c.-80C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000334315.2	F6WC43
HTR3D	ENST00000453435.1	TSL:1	c.-46C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000389268.1	Q70Z44-3
HTR3D	ENST00000382489.3	TSL:1	c.236C>G	p.Ser79Cys	missense	Exon 2 of 8	ENSP00000371929.3	Q70Z44-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000632

AC:

AN:

158182

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000286

AC:

AN:

1399746

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690374

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31600

American (AMR)

AF:

0.00

AC:

AN:

35706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.0000560

AC:

AN:

35736

South Asian (SAS)

AF:

0.00

AC:

AN:

79228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49482

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1079006

Other (OTH)

AF:

0.0000344

AC:

AN:

58104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.36

CADD

Benign

8.3

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.22

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.27

M_CAP

Benign

0.018

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.63

MutationAssessor

Benign

0.0

PhyloP100

0.51

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.31

Sift

Uncertain

0.0090

Sift4G

Benign

0.063

Polyphen

0.98

Vest4

0.34

MutPred

0.61

Loss of sheet (P = 0.1158)

MVP

0.55

MPC

0.60

ClinPred

0.39

GERP RS

0.69

PromoterAI

-0.0042

Neutral

(source)

Varity_R

0.61

gMVP

0.071

Mutation Taster

=55/45

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over