1-23193520-G-C

Position:

• chr1-23193520-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000864.5(HTR1D):​c.700C>G​(p.Leu234Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HTR1D NM_000864.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.142

Genes affected

HTR1D (HGNC:5289): (5-hydroxytryptamine receptor 1D) Enables G protein-coupled serotonin receptor activity. Involved in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway and intestine smooth muscle contraction. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08337039).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR1D	NM_000864.5	c.700C>G	p.Leu234Val	missense_variant	2/2	ENST00000374619.2	NP_000855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR1D	ENST00000374619.2	c.700C>G	p.Leu234Val	missense_variant	2/2	6	NM_000864.5	ENSP00000363748.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461720 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727144

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Nov 30, 2021

The c.700C>G (p.L234V) alteration is located in exon 1 (coding exon 1) of the HTR1D gene. This alteration results from a C to G substitution at nucleotide position 700, causing the leucine (L) at amino acid position 234 to be replaced by a valine (V). 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	0.060
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Benign	0.90
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.11
Sift	Benign	0.46	T
Sift4G	Benign	0.52	T
Polyphen		0.0010	B
Vest4		0.044
MutPred		0.37		Gain of ubiquitination at K237 (P = 0.0513);
MVP		0.45
MPC		0.12
ClinPred		0.15	T
GERP RS		4.4
Varity_R		0.073
gMVP		0.12

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: chr1-23520013;