rs39830

Positions:

• chr5-132865726-G-A
• chr5-132865726-G-C
• chr5-132865726-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005260.7(GDF9):​c.-1193C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,974 control chromosomes in the GnomAD database, including 19,537 homozygotes. 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: 𝑓 0.49 (19536 hom., cov: 31)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: GDF9 NM_005260.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420

Genes affected

GDF9 (HGNC:4224): (growth differentiation factor 9) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein regulates ovarian function. Reduced expression of this gene may be associated with polycystic ovary syndrome and mutations in this gene may be more common in mothers of dizygotic twins. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDF9	NM_005260.7	c.-1193C>T		5_prime_UTR_variant	1/2	ENST00000687138.1	NP_005251.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDF9	ENST00000687138.1	c.-1193C>T		5_prime_UTR_variant	1/2		NM_005260.7	ENSP00000510441.1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75064 AN: 151846 Hom.: 19535 Cov.: 31

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.496

GnomAD4 exome AF: 0.500 AC: 5 AN: 10 Hom.: 1 AF XY: 0.500 AC XY: 4 AN XY: 8

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.750

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.494 AC: 75098 AN: 151964 Hom.: 19536 Cov.: 31 AF XY: 0.493 AC XY: 36604 AN XY: 74262

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.598

Gnomad4 EAS AF: 0.319

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.498

Alfa AF: 0.564 Hom.: 40739

Bravo AF: 0.482

Asia WGS AF: 0.469 AC: 1630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.7
DANN	Benign	0.62

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: rs39830; hg19: chr5-132201418;