10-90743643-G-A

Variant names:

• chr10-90743643-G-A
• rs33954285
• NM_019859.4:c.1343C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_019859.4(HTR7):​c.1343C>T​(p.Pro448Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,613,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. P448R) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000055 (0 hom.)
• Consequence: HTR7 NM_019859.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12
• Publications: 10 publications found

Genes affected

HTR7 (HGNC:5302): (5-hydroxytryptamine receptor 7) The neurotransmitter, serotonin, is thought to play a role in various cognitive and behavioral functions. The serotonin receptor encoded by this gene belongs to the superfamily of G protein-coupled receptors and the gene is a candidate locus for involvement in autistic disorder and other neuropsychiatric disorders. Three splice variants have been identified which encode proteins that differ in the length of their carboxy terminal ends. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04305619).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019859.4. 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
	HTR7	NM_019859.4	MANE Select	c.1343C>T	p.Pro448Leu	missense	Exon 3 of 4	NP_062873.1	P34969-1
	HTR7	NM_000872.5		c.1296-1115C>T		intron	N/A	NP_000863.1	P34969-2
	HTR7	NM_019860.4		c.*2-1115C>T		intron	N/A	NP_062874.1	P34969-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR7	ENST00000336152.8	TSL:1 MANE Select	c.1343C>T	p.Pro448Leu	missense	Exon 3 of 4	ENSP00000337949.3	P34969-1
	HTR7	ENST00000277874.10	TSL:1	c.1296-1115C>T		intron	N/A	ENSP00000277874.6	P34969-2
	HTR7	ENST00000371719.2	TSL:1	c.*2-1115C>T		intron	N/A	ENSP00000360784.2	P34969-3

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152086 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000107 AC: 27 AN: 251380 AF XY: 0.0000957

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000616

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000547 AC: 80 AN: 1461706 Hom.: 0 Cov.: 31 AF XY: 0.0000550 AC XY: 40 AN XY: 727150

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.000403 AC: 18 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.0000432 AC: 48 AN: 1111872

Other (OTH) AF: 0.000166 AC: 10 AN: 60386

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152086 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74290

African (AFR) AF: 0.0000483 AC: 2 AN: 41404

American (AMR) AF: 0.0000655 AC: 1 AN: 15262

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000215 Hom.: 6

Bravo AF: 0.0000831

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.10
DANN	Benign	0.89
DEOGEN2	Benign	0.14	T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.1
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.034
Sift	Benign	0.057	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.29		Loss of catalytic residue at P447 (P = 0.016)
MVP		0.61
MPC		0.42
ClinPred		0.035	T
GERP RS		-3.8
Varity_R		0.026
gMVP		0.15
Mutation Taster		=100/0	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: rs33954285; hg19: chr10-92503400; COSMIC: COSV53292379;