NM_019859.4:c.701G>A

Variant names:

• chr10-90749433-C-T
• rs1564668447
• NM_019859.4:c.701G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_019859.4(HTR7):​c.701G>A​(p.Ser234Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HTR7 NM_019859.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.16
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.701G>A	p.Ser234Asn	missense	Exon 2 of 4	NP_062873.1	P34969-1
	HTR7	NM_000872.5		c.701G>A	p.Ser234Asn	missense	Exon 2 of 3	NP_000863.1	P34969-2
	HTR7	NM_019860.4		c.701G>A	p.Ser234Asn	missense	Exon 2 of 3	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.701G>A	p.Ser234Asn	missense	Exon 2 of 4	ENSP00000337949.3	P34969-1
	HTR7	ENST00000277874.10	TSL:1	c.701G>A	p.Ser234Asn	missense	Exon 2 of 3	ENSP00000277874.6	P34969-2
	HTR7	ENST00000371719.2	TSL:1	c.701G>A	p.Ser234Asn	missense	Exon 2 of 3	ENSP00000360784.2	P34969-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		6.2
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.15
Sift	Benign	0.15	T
Sift4G	Benign	0.25	T
Polyphen		0.97	D
Vest4		0.64
MutPred		0.58		Loss of ubiquitination at K229 (P = 0.0853)
MVP		0.76
MPC		1.1
ClinPred		0.96	D
GERP RS		5.3
Varity_R		0.58
gMVP		0.86
Mutation Taster		=40/60	disease causing

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: rs1564668447; hg19: chr10-92509190;