chr7-144397467-G-T

Variant names:

• chr7-144397467-G-T
• rs139083352
• NM_001080413.3:c.1849C>A

Variant summary

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

The NM_001080413.3(NOBOX):​c.1849C>A​(p.His617Asn) 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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NOBOX NM_001080413.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172

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=0.068201035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOBOX	NM_001080413.3	c.1849C>A	p.His617Asn	missense_variant	Exon 10 of 10	ENST00000467773.1	NP_001073882.3
NOBOX	XM_017011742.3	c.1753C>A	p.His585Asn	missense_variant	Exon 10 of 10		XP_016867231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOBOX	ENST00000467773.1	c.1849C>A	p.His617Asn	missense_variant	Exon 10 of 10	5	NM_001080413.3	ENSP00000419457.1
NOBOX	ENST00000483238.5	c.1753C>A	p.His585Asn	missense_variant	Exon 10 of 10	5		ENSP00000419565.1
NOBOX	ENST00000645489.1	c.1498C>A	p.His500Asn	missense_variant	Exon 8 of 8			ENSP00000496732.1
NOBOX	ENST00000643164.1	c.*44C>A		downstream_gene_variant				ENSP00000495343.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	9.4
DANN	Benign	0.79
DEOGEN2	Benign	0.11	.;.;T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.63	T;T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.068	T;T;T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.8	.;.;L
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.4	.;N;N
REVEL	Benign	0.13
Sift	Benign	0.052	.;T;T
Sift4G	Benign	0.45	.;T;T
Vest4		0.37, 0.20
MutPred		0.16		.;.;Loss of catalytic residue at H617 (P = 0.4157);
MVP		0.63
MPC		0.048
ClinPred		0.041	T
GERP RS		0.48
Varity_R		0.051
gMVP		0.11

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: rs139083352; hg19: chr7-144094560;