dbSNP rs781992710: FIGLA:p.Gly6ArgfsTer66 (chr2-70790602-CGGCGCGGGGATCTAGGACGCCG-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 5P and 4B. PVS1_StrongPP5BS2

The NM_001004311.3(FIGLA):c.15_36delCGGCGTCCTAGATCCCCGCGCC(p.Gly6ArgfsTer66) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000121 in 1,317,352 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

FIGLA
NM_001004311.3 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.34

Publications

5 publications found

Variant links:

Genes affected

FIGLA (HGNC:24669): (folliculogenesis specific bHLH transcription factor) This gene encodes a protein that functions in postnatal oocyte-specific gene expression. The protein is a basic helix-loop-helix transcription factor that regulates multiple oocyte-specific genes, including genes involved in folliculogenesis and those that encode the zona pellucida. Mutations in this gene cause premature ovarian failure type 6. [provided by RefSeq, Sep 2009]

FIGLA Gene-Disease associations (from GenCC):

premature ovarian failure 6
Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

FIGLA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 4 pathogenic variants in the truncated region.

PP5

Variant 2-70790602-CGGCGCGGGGATCTAGGACGCCG-C is Pathogenic according to our data. Variant chr2-70790602-CGGCGCGGGGATCTAGGACGCCG-C is described in ClinVar as [Pathogenic]. Clinvar id is 2137.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAdExome4 at 16 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIGLA	NM_001004311.3 link	c.15_36delCGGCGTCCTAGATCCCCGCGCC	p.Gly6ArgfsTer66	frameshift_variant	Exon 1 of 5	ENST00000332372.6	NP_001004311.2	Q6QHK4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIGLA	ENST00000332372.6 link	c.15_36delCGGCGTCCTAGATCCCCGCGCC	p.Gly6ArgfsTer66	frameshift_variant	Exon 1 of 5	1	NM_001004311.3	ENSP00000333097.6		Q6QHK4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000136

AC:

AN:

73466

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000121

AC:

AN:

1317352

Hom.:

AF XY:

0.0000124

AC XY:

AN XY:

646388

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26904

American (AMR)

AF:

0.00

AC:

AN:

28294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22022

East Asian (EAS)

AF:

0.00

AC:

AN:

30098

South Asian (SAS)

AF:

0.0000433

AC:

AN:

69248

European-Finnish (FIN)

AF:

0.0000305

AC:

AN:

32760

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4304

European-Non Finnish (NFE)

AF:

0.0000105

AC:

AN:

1048802

Other (OTH)

AF:

0.0000182

AC:

AN:

54920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.419

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000971

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Premature ovarian failure 6

Pathogenic:1

Jun 01, 2008

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.3

Mutation Taster

=40/160

disease causing (ClinVar)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs781992710

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over