7-144401899-G-C

Position:

• chr7-144401899-G-C

Variant summary

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

The NM_001080413.3(NOBOX):​c.262C>G​(p.Leu88Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L88L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NOBOX NM_001080413.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146

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=0.09527552).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOBOX	NM_001080413.3	c.262C>G	p.Leu88Val	missense_variant	3/10	ENST00000467773.1	NP_001073882.3
NOBOX	XM_017011742.3	c.262C>G	p.Leu88Val	missense_variant	3/10		XP_016867231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOBOX	ENST00000467773.1	c.262C>G	p.Leu88Val	missense_variant	3/10	5	NM_001080413.3	ENSP00000419457.1
NOBOX	ENST00000483238.5	c.262C>G	p.Leu88Val	missense_variant	3/10	5		ENSP00000419565.1
NOBOX	ENST00000645489.1	c.38-302C>G		intron_variant				ENSP00000496732.1
NOBOX	ENST00000643164.1	c.38-1587C>G		intron_variant				ENSP00000495343.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459798 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726298

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

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.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	1.2
DANN	Benign	0.94
DEOGEN2	Benign	0.039	.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.095	T;T
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Benign	0.55	N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.030	N;N
REVEL	Benign	0.18
Sift	Benign	0.27	T;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.42	.;B
Vest4		0.12
MutPred		0.082		Gain of methylation at K92 (P = 0.0699);Gain of methylation at K92 (P = 0.0699);
MVP		0.72
MPC		0.022
ClinPred		0.088	T
GERP RS		-0.10
Varity_R		0.038
gMVP		0.019

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: rs727714; hg19: chr7-144098992;