rs2699503

Positions:

• chr7-144398507-A-C
• chr7-144398507-A-G
• chr7-144398507-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080413.3(NOBOX):​c.1549T>G​(p.Phe517Val) 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. 14/20 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. F517L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: NOBOX NM_001080413.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77

Genes affected

NOBOX (HGNC:22448): (NOBOX oogenesis homeobox) This homeobox gene encodes a transcription factor that is thought to play a role in oogenesis. In mice, it is essential for folliculogenesis and regulation of oocyte-specific genes. Defects in this gene result in premature ovarian failure type 5.[provided by RefSeq, May 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16502291).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOBOX	NM_001080413.3	c.1549T>G	p.Phe517Val	missense_variant	9/10	ENST00000467773.1	NP_001073882.3
NOBOX	XM_017011742.3	c.1453T>G	p.Phe485Val	missense_variant	9/10		XP_016867231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOBOX	ENST00000467773.1	c.1549T>G	p.Phe517Val	missense_variant	9/10	5	NM_001080413.3	ENSP00000419457.1
NOBOX	ENST00000483238.5	c.1453T>G	p.Phe485Val	missense_variant	9/10	5		ENSP00000419565.1
NOBOX	ENST00000645489.1	c.1198T>G	p.Phe400Val	missense_variant	7/8			ENSP00000496732.1
NOBOX	ENST00000643164.1	c.646T>G	p.Phe216Val	missense_variant	6/7			ENSP00000495343.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.22	.;.;T;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.64	T;T;T;T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	2.0	.;.;M;.
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.6	.;D;D;.
REVEL	Benign	0.061
Sift	Pathogenic	0.0	.;D;D;.
Sift4G	Benign	0.10	.;T;T;.
Vest4		0.26, 0.27
MutPred		0.26		.;.;Gain of glycosylation at S520 (P = 0.0866);.;
MVP		0.53
MPC		0.16
ClinPred		0.80	D
GERP RS		3.0
Varity_R		0.21
gMVP		0.29

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

LitVar

Other links and lift over

dbSNP: rs2699503; hg19: chr7-144095600;