5-132861830-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_005260.7(GDF9):c.1124A>T(p.His375Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,613,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_005260.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GDF9 | NM_005260.7 | c.1124A>T | p.His375Leu | missense_variant | 2/2 | ENST00000687138.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GDF9 | ENST00000687138.1 | c.1124A>T | p.His375Leu | missense_variant | 2/2 | NM_005260.7 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152204Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251464Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135914
GnomAD4 exome AF: 0.0000369 AC: 54AN: 1461768Hom.: 0 Cov.: 30 AF XY: 0.0000399 AC XY: 29AN XY: 727214
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74364
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 10, 2022 | The c.1124A>T (p.H375L) alteration is located in exon 2 (coding exon 2) of the GDF9 gene. This alteration results from a A to T substitution at nucleotide position 1124, causing the histidine (H) at amino acid position 375 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at