19-38384432-G-A
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PVS1_ModerateBP6_Very_StrongBS2
The NM_152657.4(GGN):c.1939C>T(p.Gln647Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.0115 in 1,613,516 control chromosomes in the GnomAD database, including 143 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0079 ( 9 hom., cov: 32)
Exomes 𝑓: 0.012 ( 134 hom. )
Consequence
GGN
NM_152657.4 stop_gained
NM_152657.4 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 3.65
Genes affected
GGN (HGNC:18869): (gametogenetin) This gene is a germ cell-specific gene that encodes proteins that interact with POG (proliferation of germ cells). Alternatively spliced transcript variants of a similar mouse gene encode at least three different proteins, namely gametogenetin protein 1a, gametogenetin protein 2, and gametogenetin protein 3, which show a perinuclear, cytoplasmic, and nucleolar localization, respectively. These proteins regulate the localization of POG and may play a role in spermatogenesis. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0102 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
BP6
Variant 19-38384432-G-A is Benign according to our data. Variant chr19-38384432-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 769973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAd4 at 9 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GGN | NM_152657.4 | c.1939C>T | p.Gln647Ter | stop_gained | 4/4 | ENST00000334928.11 | |
GGN | XM_005258619.5 | c.1939C>T | p.Gln647Ter | stop_gained | 4/4 | ||
GGN | XM_017026451.2 | c.1939C>T | p.Gln647Ter | stop_gained | 3/3 | ||
GGN | XM_011526603.3 | c.1690C>T | p.Gln564Ter | stop_gained | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GGN | ENST00000334928.11 | c.1939C>T | p.Gln647Ter | stop_gained | 4/4 | 1 | NM_152657.4 | P1 | |
GGN | ENST00000591809.5 | n.290C>T | non_coding_transcript_exon_variant | 4/4 | 1 | ||||
GGN | ENST00000585737.1 | c.*170C>T | 3_prime_UTR_variant, NMD_transcript_variant | 5/5 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00790 AC: 1202AN: 152192Hom.: 9 Cov.: 32
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GnomAD3 exomes AF: 0.00815 AC: 2048AN: 251244Hom.: 18 AF XY: 0.00846 AC XY: 1149AN XY: 135792
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GnomAD4 exome AF: 0.0118 AC: 17295AN: 1461206Hom.: 134 Cov.: 30 AF XY: 0.0117 AC XY: 8506AN XY: 726938
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GnomAD4 genome AF: 0.00789 AC: 1201AN: 152310Hom.: 9 Cov.: 32 AF XY: 0.00764 AC XY: 569AN XY: 74488
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | GGN: BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
GGN-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 22, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Calibrated prediction
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BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
D
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at