rs186548772

Variant names:

• chr2-70777656-C-G
• rs186548772
• NM_001004311.3:c.625G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-70777656-C-G
• chr2-70777656-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001004311.3(FIGLA):​c.625G>C​(p.Val209Leu) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V209I) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FIGLA NM_001004311.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 2 publications found

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)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04722953).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIGLA	NM_001004311.3	c.625G>C	p.Val209Leu	missense_variant	Exon 4 of 5	ENST00000332372.6	NP_001004311.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIGLA	ENST00000332372.6	c.625G>C	p.Val209Leu	missense_variant	Exon 4 of 5	1	NM_001004311.3	ENSP00000333097.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 23

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	0.0018	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.047	T
MetaSVM	Uncertain	0.13	D
MutationAssessor	Benign	1.2	L
PhyloP100		0.16
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.20
Sift	Uncertain	0.019	D
Sift4G	Benign	0.065	T
Polyphen		0.13	B
Vest4		0.11
MutPred		0.12		Gain of disorder (P = 0.1961);
MVP		0.29
MPC		0.095
ClinPred		0.32	T
GERP RS		2.8
Varity_R		0.069
gMVP		0.22
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs186548772; hg19: chr2-71004788;