rs1214582093

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-77630593-C-A
• chr5-77630593-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032109.3(OTP):​c.649G>T​(p.Val217Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000071 in 1,408,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. V217M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: OTP NM_032109.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.68

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41209048).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTP	NM_032109.3	c.649G>T	p.Val217Leu	missense_variant	Exon 3 of 3	ENST00000306422.5	NP_115485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTP	ENST00000306422.5	c.649G>T	p.Val217Leu	missense_variant	Exon 3 of 3	1	NM_032109.3	ENSP00000302814.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1408178 Hom.: 0 Cov.: 30 AF XY: 0.00000143 AC XY: 1 AN XY: 697048

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000269

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.053	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.87	D
M_CAP	Pathogenic	0.88	D
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	0.17	D
MutationAssessor	Benign	1.2	L
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.23	N
REVEL	Uncertain	0.32
Sift	Benign	0.30	T
Sift4G	Benign	0.73	T
Polyphen		0.99	D
Vest4		0.32
MutPred		0.25		Loss of glycosylation at S218 (P = 0.1132);
MVP		0.73
MPC		0.86
ClinPred		0.78	D
GERP RS		3.6
Varity_R		0.16
gMVP		0.73

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-76926418;