7-155070911-T-G

Variant names:

• chr7-155070911-T-G
• rs6320
• NM_024012.4:c.12T>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_024012.4(HTR5A):​c.12T>G​(p.Pro4Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,449,068 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: HTR5A NM_024012.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.736
• Publications: 22 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=-0.736 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024012.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR5A	NM_024012.4	MANE Select	c.12T>G	p.Pro4Pro	synonymous	Exon 1 of 2	NP_076917.1
	HTR5A-AS1	NR_038945.1		n.524+123A>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR5A	ENST00000287907.3	TSL:1 MANE Select	c.12T>G	p.Pro4Pro	synonymous	Exon 1 of 2	ENSP00000287907.2
	HTR5A-AS1	ENST00000395731.5	TSL:1	n.524+123A>C		intron	N/A
	HTR5A-AS1	ENST00000493904.3	TSL:4	n.551+123A>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000124 AC: 3 AN: 242472 AF XY: 0.00000759

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000276 AC: 4 AN: 1449068 Hom.: 0 Cov.: 42 AF XY: 0.00000277 AC XY: 2 AN XY: 721020

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26026

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 86088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110612

Other (OTH) AF: 0.00 AC: 0 AN: 60234

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 640

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.9
DANN	Benign	0.77
PhyloP100		-0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs6320; hg19: chr7-154862621;