NM_032109.3:c.253G>A

Variant names:

• chr5-77637015-C-T
• rs77880799
• NM_032109.3:c.253G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032109.3(OTP):​c.253G>A​(p.Gly85Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G85E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: OTP NM_032109.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.44
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20967498).

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.253G>A	p.Gly85Arg	missense	Exon 2 of 3	NP_115485.1	Q5XKR4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTP	ENST00000306422.5	TSL:1 MANE Select	c.253G>A	p.Gly85Arg	missense	Exon 2 of 3	ENSP00000302814.3	Q5XKR4
	OTP	ENST00000515716.1	TSL:2	n.-22G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.062
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.21	T
MetaSVM	Uncertain	-0.0044	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.4
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.25
Sift	Benign	0.17	T
Sift4G	Benign	0.074	T
Polyphen		0.69	P
Vest4		0.31
MutPred		0.27		Gain of solvent accessibility (P = 0.0097)
MVP		0.41
MPC		1.1
ClinPred		0.50	T
GERP RS		5.6
Varity_R		0.22
gMVP		0.34
Mutation Taster		=76/24	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: rs77880799; hg19: chr5-76932840; COSMIC: COSV60568512; COSMIC: COSV60568512;