13-46896689-C-G

Variant names:

• chr13-46896689-C-G
• rs6312
• NM_000621.5:c.-344G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000621.5(HTR2A):​c.-344G>C variant causes a 5 prime UTR change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HTR2A NM_000621.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.91
• Publications: 32 publications found

Genes affected

HTR2A (HGNC:5293): (5-hydroxytryptamine receptor 2A) This gene encodes one of the receptors for serotonin, a neurotransmitter with many roles. Mutations in this gene are associated with susceptibility to schizophrenia and obsessive-compulsive disorder, and are also associated with response to the antidepressant citalopram in patients with major depressive disorder (MDD). MDD patients who also have a mutation in intron 2 of this gene show a significantly reduced response to citalopram as this antidepressant downregulates expression of this gene. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ENSG00000301465 (HGNC:):

ACMG classification

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=0.39590928).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000621.5. 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
	HTR2A	NM_000621.5	MANE Select	c.-344G>C		5_prime_UTR	Exon 1 of 4	NP_000612.1	P28223-1
	HTR2A	NM_001165947.5		c.-93G>C		5_prime_UTR	Exon 1 of 3	NP_001159419.2	A0A7P0PKG8
	HTR2A	NM_001378924.1		c.-328-455G>C		intron	N/A	NP_001365853.1	P28223-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2A	ENST00000542664.4	TSL:1 MANE Select	c.-344G>C		5_prime_UTR	Exon 1 of 4	ENSP00000437737.1	P28223-1
	HTR2A	ENST00000543956.5	TSL:1	c.-93G>C		5_prime_UTR	Exon 1 of 3	ENSP00000441861.2	A0A7P0PKG8
	HTR2A	ENST00000941626.1		c.-783G>C		5_prime_UTR	Exon 1 of 3	ENSP00000611685.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.92
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.86	T
PhyloP100		4.9
PROVEAN	Benign	1.6	N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Vest4		0.42
MutPred		0.72		Loss of helix (P = 0.0167)
MVP		0.54
ClinPred		0.43	T
GERP RS		4.5
PromoterAI		-0.22	Neutral
Mutation Taster		=92/8	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs6312; hg19: chr13-47470824;