chr5-77630593-C-T

Variant names:

• chr5-77630593-C-T
• rs1214582093
• NM_032109.3:c.649G>A

Variant summary

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

The NM_032109.3(OTP):​c.649G>A​(p.Val217Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000071 in 1,408,176 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: OTP NM_032109.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.68
• Publications: 0 publications found

Genes affected

OTP (HGNC:8518): (orthopedia homeobox) This gene encodes a member of the homeodomain (HD) family. HD family proteins are helix-turn-helix transcription factors that play key roles in the specification of cell fates. This protein may function during brain development. [provided by RefSeq, Jul 2008]

OTP-AS1 (HGNC:):

OTP-AS1 (HGNC:58154):

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_032109.3. 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
	OTP	NM_032109.3	MANE Select	c.649G>A	p.Val217Met	missense	Exon 3 of 3	NP_115485.1	Q5XKR4
	OTP-AS1	NR_198942.1		n.91+832C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTP	ENST00000306422.5	TSL:1 MANE Select	c.649G>A	p.Val217Met	missense	Exon 3 of 3	ENSP00000302814.3	Q5XKR4
	OTP-AS1	ENST00000851058.1		n.91+832C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000631 AC: 1 AN: 158416 AF XY: 0.0000114

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000226

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1408176 Hom.: 0 Cov.: 30 AF XY: 0.00000143 AC XY: 1 AN XY: 697046

African (AFR) AF: 0.00 AC: 0 AN: 32252

American (AMR) AF: 0.00 AC: 0 AN: 38638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25292

East Asian (EAS) AF: 0.00 AC: 0 AN: 37226

South Asian (SAS) AF: 0.00 AC: 0 AN: 81378

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5620

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1091122

Other (OTH) AF: 0.0000171 AC: 1 AN: 58618

GnomAD4 genome Cov.: 33

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	Benign	0.18
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.86	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Uncertain	0.47	D
MutationAssessor	Benign	1.5	L
PhyloP100		4.7
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	0.15	N
REVEL	Uncertain	0.34
Sift	Benign	0.15	T
Sift4G	Benign	0.32	T
Polyphen		1.0	D
Vest4		0.33
MutPred		0.22		Gain of disorder (P = 0.0975)
MVP		0.74
MPC		0.92
ClinPred		0.79	D
GERP RS		3.6
Varity_R		0.13
gMVP		0.72
Mutation Taster		=61/39	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: rs1214582093; hg19: chr5-76926418;