7-144398507-A-T

Variant names:

• chr7-144398507-A-T
• rs2699503
• NM_001080413.3:c.1549T>A

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/21 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
• Publications: 27 publications found

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]

NOBOX Gene-Disease associations (from GenCC):

• premature ovarian failure 5

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

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=0.15041709).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080413.3. 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
	NOBOX	NM_001080413.3	MANE Select	c.1549T>A	p.Phe517Ile	missense	Exon 9 of 10	NP_001073882.3	O60393-1
	NOBOX	NM_001436401.1		c.1198T>A	p.Phe400Ile	missense	Exon 7 of 8	NP_001423330.1	A0A2R8Y8C8
	NOBOX	NM_001436402.1		c.646T>A	p.Phe216Ile	missense	Exon 6 of 7	NP_001423331.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOBOX	ENST00000467773.1	TSL:5 MANE Select	c.1549T>A	p.Phe517Ile	missense	Exon 9 of 10	ENSP00000419457.1	O60393-1
	NOBOX	ENST00000645489.2		c.1198T>A	p.Phe400Ile	missense	Exon 7 of 8	ENSP00000496732.1
	NOBOX	ENST00000643164.2		c.646T>A	p.Phe216Ile	missense	Exon 6 of 7	ENSP00000495343.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 29775

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.8
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.026
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.078	T
Vest4		0.30
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
Mutation Taster		=94/6	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: rs2699503; hg19: chr7-144095600;