rs201948885

Variant names:

• chr3-184100632-T-A
• rs201948885
• NM_001256613.2:c.215T>A

Your query was ambiguous. Multiple possible variants found:

• chr3-184100632-T-A
• chr3-184100632-T-C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001256613.2(HTR3E):​c.215T>A​(p.Met72Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,613,876 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. M72T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: HTR3E NM_001256613.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.04
• Publications: 0 publications found

Genes affected

HTR3E (HGNC:24005): (5-hydroxytryptamine receptor 3E) This locus encodes a 5-hydroxytryptamine (serotonin) receptor subunit. The encoded protein, subunit E, may play a role in neurotransmission in myenteric neurons. Genes encoding subunits C, D and E form a cluster on chromosome 3. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Feb 2012]

HTR3E-AS1 (HGNC:41032): (HTR3E antisense RNA 1)

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.969

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256613.2. 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
	HTR3E	NM_001256613.2	MANE Select	c.215T>A	p.Met72Lys	missense	Exon 2 of 9	NP_001243542.1	A5X5Y0-1
	HTR3E	NM_001256614.1		c.260T>A	p.Met87Lys	missense	Exon 1 of 7	NP_001243543.1	A5X5Y0-6
	HTR3E	NM_182589.2		c.260T>A	p.Met87Lys	missense	Exon 1 of 8	NP_872395.2	A5X5Y0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3E	ENST00000415389.6	TSL:1 MANE Select	c.215T>A	p.Met72Lys	missense	Exon 2 of 9	ENSP00000401444.2	A5X5Y0-1
	HTR3E	ENST00000440596.2	TSL:1	c.260T>A	p.Met87Lys	missense	Exon 1 of 7	ENSP00000406050.2	A5X5Y0-6
	HTR3E	ENST00000335304.6	TSL:1	c.260T>A	p.Met87Lys	missense	Exon 1 of 8	ENSP00000335511.2	A5X5Y0-3

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152106 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251102 AF XY: 0.00000737

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461770 Hom.: 0 Cov.: 36 AF XY: 0.00000275 AC XY: 2 AN XY: 727194

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111936

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152106 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74298

African (AFR) AF: 0.0000966 AC: 4 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.40	T
Eigen	Benign	0.061
Eigen_PC	Benign	0.091
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.055	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.0
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.62
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.63	P
Vest4		0.58
MutPred		0.75		Loss of stability (P = 0.012)
MVP		0.84
MPC		0.15
ClinPred		0.92	D
GERP RS		3.8
PromoterAI		-0.081	Neutral
Varity_R		0.74
gMVP		0.49
Mutation Taster		=91/9	polymorphism

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: rs201948885; hg19: chr3-183818420;