10-90743643-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019859.4(HTR7):​c.1343C>A​(p.Pro448Gln) 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. 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: not found (cov: 32)
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04314643).

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>A	p.Pro448Gln	missense	Exon 3 of 4	NP_062873.1	P34969-1
	HTR7	NM_000872.5		c.1296-1115C>A		intron	N/A	NP_000863.1	P34969-2
	HTR7	NM_019860.4		c.*2-1115C>A		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>A	p.Pro448Gln	missense	Exon 3 of 4	ENSP00000337949.3	P34969-1
	HTR7	ENST00000277874.10	TSL:1	c.1296-1115C>A		intron	N/A	ENSP00000277874.6	P34969-2
	HTR7	ENST00000371719.2	TSL:1	c.*2-1115C>A		intron	N/A	ENSP00000360784.2	P34969-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.053
DANN	Benign	0.40
DEOGEN2	Benign	0.14	T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.1
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.053
Sift	Benign	0.79	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.15
MutPred		0.086		Loss of catalytic residue at P447 (P = 0.016)
MVP		0.45
MPC		0.38
ClinPred		0.022	T
GERP RS		-3.8
Varity_R		0.027
gMVP		0.12
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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;