3-184100628-G-C

Variant names:

• chr3-184100628-G-C
• rs7627615
• NM_001256613.2:c.211G>C

Variant summary

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

The NM_001256613.2(HTR3E):​c.211G>C​(p.Ala71Pro) 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 benign outcome for this variant. 14/21 in silico tools predict a benign 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. A71T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HTR3E NM_001256613.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.49

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

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=0.26337034).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR3E	NM_001256613.2	c.211G>C	p.Ala71Pro	missense_variant	Exon 2 of 9	ENST00000415389.6	NP_001243542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR3E	ENST00000415389.6	c.211G>C	p.Ala71Pro	missense_variant	Exon 2 of 9	1	NM_001256613.2	ENSP00000401444.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251206 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135798

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461870 Hom.: 0 Cov.: 54 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

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.: 30

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T;.;.;.;.
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.39	T;T;T;T;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.26	T;T;T;T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.2	L;L;.;.;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.1	N;N;N;N;N
REVEL	Benign	0.25
Sift	Uncertain	0.029	D;D;T;T;T
Sift4G	Uncertain	0.027	D;D;D;D;D
Polyphen		0.32	B;B;P;P;.
Vest4		0.23
MutPred		0.68		Loss of catalytic residue at A71 (P = 0.0646);Loss of catalytic residue at A71 (P = 0.0646);.;.;.;
MVP		0.73
MPC		0.13
ClinPred		0.61	D
GERP RS		2.6
Varity_R		0.28
gMVP		0.32

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

LitVar

Other links and lift over

dbSNP: rs7627615; hg19: chr3-183818416;