7-144401541-G-C

Variant names:

• chr7-144401541-G-C
• NM_001080413.3:c.349C>G

Variant summary

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

The NM_001080413.3(NOBOX):​c.349C>G​(p.Arg117Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000734 in 1,362,778 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: NOBOX NM_001080413.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

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=0.099730045).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOBOX	NM_001080413.3	c.349C>G	p.Arg117Gly	missense_variant	Exon 4 of 10	ENST00000467773.1	NP_001073882.3
NOBOX	XM_017011742.3	c.349C>G	p.Arg117Gly	missense_variant	Exon 4 of 10		XP_016867231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOBOX	ENST00000467773.1	c.349C>G	p.Arg117Gly	missense_variant	Exon 4 of 10	5	NM_001080413.3	ENSP00000419457.1
NOBOX	ENST00000483238.5	c.349C>G	p.Arg117Gly	missense_variant	Exon 4 of 10	5		ENSP00000419565.1
NOBOX	ENST00000645489.1	c.94C>G	p.Arg32Gly	missense_variant	Exon 2 of 8			ENSP00000496732.1
NOBOX	ENST00000643164.1	c.38-1229C>G		intron_variant	Intron 1 of 6			ENSP00000495343.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.34e-7 AC: 1 AN: 1362778 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 667760

Gnomad4 AFR exome AF: 0.00

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: 0.0000178

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.13	.;.;T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.47	T;T;T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	0.34	.;N;N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.8	.;N;N
REVEL	Benign	0.19
Sift	Uncertain	0.0030	.;D;D
Sift4G	Benign	0.075	.;T;T
Polyphen		0.093	.;.;B
Vest4		0.30, 0.21
MutPred		0.18		.;Gain of glycosylation at S119 (P = 0.0876);Gain of glycosylation at S119 (P = 0.0876);
MVP		0.78
MPC		0.027
ClinPred		0.15	T
GERP RS		3.5
Varity_R		0.093
gMVP		0.051

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-144098634;