6-77462241-C-T

Position:

• chr6-77462241-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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

Verdict is Uncertain_significance. Variant got 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR1B	NM_000863.3	c.1163G>A	p.Cys388Tyr	missense_variant	1/1	ENST00000369947.5	NP_000854.1
LOC105377864	XM_047419659.1	c.-11983C>T		5_prime_UTR_variant	1/6		XP_047275615.1
LOC105377864	XM_047419660.1	c.-3742-12285C>T		intron_variant			XP_047275616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR1B	ENST00000369947.5	c.1163G>A	p.Cys388Tyr	missense_variant	1/1	6	NM_000863.3	ENSP00000358963.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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

Dec 05, 2024

The c.1163G>A (p.C388Y) alteration is located in exon 1 (coding exon 1) of the HTR1B gene. This alteration results from a G to A substitution at nucleotide position 1163, causing the cysteine (C) at amino acid position 388 to be replaced by a tyrosine (Y). 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	0.096
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
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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-78171958;