rs564572933

Variant names:

• chr7-155071104-C-A
• rs564572933
• NM_024012.4:c.205C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-155071104-C-A
• chr7-155071104-C-G
• chr7-155071104-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_024012.4(HTR5A):​c.205C>A​(p.Arg69Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R69G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HTR5A NM_024012.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.03
• Publications: 1 publications found

Genes affected

HTR5A (HGNC:5300): (5-hydroxytryptamine receptor 5A) The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has been implicated in a wide range of psychiatric conditions and also has vasoconstrictive and vasodilatory effects. The gene described in this record is a member of 5-hydroxytryptamine (serotonin) receptor family and encodes a multi-pass membrane protein that functions as a receptor for 5-hydroxytryptamine and couples to G-proteins. This protein has been shown to function in part through the regulation of intracellular Ca2+ mobilization. [provided by RefSeq, Jul 2008]

HTR5A-AS1 (HGNC:48956): (HTR5A antisense RNA 1)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.934

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR5A	NM_024012.4	c.205C>A	p.Arg69Ser	missense_variant	Exon 1 of 2	ENST00000287907.3	NP_076917.1
HTR5A-AS1	NR_038945.1	n.454G>T		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR5A	ENST00000287907.3	c.205C>A	p.Arg69Ser	missense_variant	Exon 1 of 2	1	NM_024012.4	ENSP00000287907.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D;D
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Benign	0.59	D
LIST_S2	Uncertain	0.94	.;D
M_CAP	Benign	0.048	D
MetaRNN	Pathogenic	0.93	D;D
MetaSVM	Benign	-0.59	T
MutationAssessor	Pathogenic	3.0	M;M
PhyloP100		3.0
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-5.1	D;.
REVEL	Uncertain	0.46
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.0020	D;.
Polyphen		1.0	D;D
Vest4		0.82
MutPred		0.79		Loss of methylation at R69 (P = 0.0385);Loss of methylation at R69 (P = 0.0385);
MVP		0.78
MPC		1.2
ClinPred		1.0	D
GERP RS		4.4
Varity_R		0.85
gMVP		0.81
Mutation Taster		=45/55	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

dbSNP: rs564572933; hg19: chr7-154862814;