7-144398507-A-T

Position:

• 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>A​(p.Phe517Ile) 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. 13/20 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=0.15041709).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOBOX	NM_001080413.3	c.1549T>A	p.Phe517Ile	missense_variant	9/10	ENST00000467773.1	NP_001073882.3
NOBOX	XM_017011742.3	c.1453T>A	p.Phe485Ile	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>A	p.Phe517Ile	missense_variant	9/10	5	NM_001080413.3	ENSP00000419457.1
NOBOX	ENST00000483238.5	c.1453T>A	p.Phe485Ile	missense_variant	9/10	5		ENSP00000419565.1
NOBOX	ENST00000645489.1	c.1198T>A	p.Phe400Ile	missense_variant	7/8			ENSP00000496732.1
NOBOX	ENST00000643164.1	c.646T>A	p.Phe216Ile	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	0.19
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	.;.;T;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.64	T;T;T;T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	.;.;M;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.3	.;N;N;.
REVEL	Benign	0.026
Sift	Uncertain	0.0010	.;D;D;.
Sift4G	Benign	0.078	.;T;T;.
Vest4		0.30, 0.32
MutPred		0.26		.;.;Gain of glycosylation at S520 (P = 0.1125);.;
MVP		0.50
MPC		0.17
ClinPred		0.55	D
GERP RS		3.0
Varity_R		0.17
gMVP		0.30

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;