rs2053901501

Variant names:

• chr7-144397486-G-A
• rs2053901501
• NM_001080413.3:c.1830C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-144397486-G-A
• chr7-144397486-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001080413.3(NOBOX):​c.1830C>T​(p.Phe610Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,384,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: NOBOX NM_001080413.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=1.85 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOBOX	NM_001080413.3	c.1830C>T	p.Phe610Phe	synonymous_variant	Exon 10 of 10	ENST00000467773.1	NP_001073882.3
NOBOX	NM_001436401.1	c.1479C>T	p.Phe493Phe	synonymous_variant	Exon 8 of 8		NP_001423330.1
NOBOX	NM_001436402.1	c.927C>T	p.Phe309Phe	synonymous_variant	Exon 7 of 7		NP_001423331.1
NOBOX	XM_017011742.3	c.1734C>T	p.Phe578Phe	synonymous_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.1830C>T	p.Phe610Phe	synonymous_variant	Exon 10 of 10	5	NM_001080413.3	ENSP00000419457.1
NOBOX	ENST00000483238.5	c.1734C>T	p.Phe578Phe	synonymous_variant	Exon 10 of 10	5		ENSP00000419565.1
NOBOX	ENST00000645489.1	c.1479C>T	p.Phe493Phe	synonymous_variant	Exon 8 of 8			ENSP00000496732.1
NOBOX	ENST00000643164.1	c.*25C>T		downstream_gene_variant				ENSP00000495343.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1384760 Hom.: 0 Cov.: 31 AF XY: 0.00000146 AC XY: 1 AN XY: 683300

African (AFR) AF: 0.00 AC: 0 AN: 31592

American (AMR) AF: 0.00 AC: 0 AN: 35684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25164

East Asian (EAS) AF: 0.00 AC: 0 AN: 35732

South Asian (SAS) AF: 0.00 AC: 0 AN: 79226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34992

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078766

Other (OTH) AF: 0.00 AC: 0 AN: 57910

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.56
PhyloP100		1.8

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: rs2053901501; hg19: chr7-144094579;