6-77462241-C-T

Variant names:

• chr6-77462241-C-T
• NM_000863.3:c.1163G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1 PM2

The NM_000863.3(HTR1B):​c.1163G>A​(p.Cys388Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C388R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HTR1B NM_000863.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.13
• Publications: 0 publications found

Genes affected

HTR1B (HGNC:5287): (5-hydroxytryptamine receptor 1B) The protein encoded by this intronless gene is a G-protein coupled receptor for serotonin (5-hydroxytryptamine). Ligand binding activates second messengers that inhibit the activity of adenylate cyclase and manage the release of serotonin, dopamine, and acetylcholine in the brain. The encoded protein may be involved in several neuropsychiatric disorders and therefore is often a target of antidepressant and other psychotherapeutic drugs. [provided by RefSeq, Nov 2015]

LOC105377864 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM1: In a lipid_moiety_binding_region S-palmitoyl cysteine (size 0) in uniprot entity 5HT1B_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000863.3. 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
	HTR1B	NM_000863.3	MANE Select	c.1163G>A	p.Cys388Tyr	missense	Exon 1 of 1	NP_000854.1	P28222

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR1B	ENST00000369947.5	TSL:6 MANE Select	c.1163G>A	p.Cys388Tyr	missense	Exon 1 of 1	ENSP00000358963.3	P28222
	ENSG00000296734	ENST00000741460.1		n.48+4659G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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	0.096
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		7.1
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.21
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.018	D
Polyphen		0.84	P
Vest4		0.67
MutPred		0.48		Gain of disorder (P = 0.0619)
MVP		0.61
MPC		1.8
ClinPred		0.84	D
GERP RS		5.3
Varity_R		0.42
gMVP		0.95
Mutation Taster		=44/56	disease causing

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

Other links and lift over

hg19: chr6-78171958;