17-36581492-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_024835.5(GGNBP2):​c.1169C>G​(p.Pro390Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

GGNBP2
NM_024835.5 missense

Scores

2
5
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.79
Variant links:
Genes affected
GGNBP2 (HGNC:19357): (gametogenetin binding protein 2) Predicted to be involved in spermatogenesis. Predicted to act upstream of or within several processes, including labyrinthine layer blood vessel development; negative regulation of cell population proliferation; and negative regulation of protein phosphorylation. Predicted to be located in cytoplasmic vesicle. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27017623).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GGNBP2NM_024835.5 linkc.1169C>G p.Pro390Arg missense_variant Exon 9 of 14 ENST00000613102.5 NP_079111.1 Q9H3C7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GGNBP2ENST00000613102.5 linkc.1169C>G p.Pro390Arg missense_variant Exon 9 of 14 1 NM_024835.5 ENSP00000478220.1 Q9H3C7-1
GGNBP2ENST00000617860.4 linkn.2512C>G non_coding_transcript_exon_variant Exon 8 of 8 2
GGNBP2ENST00000618837.4 linkn.1441C>G non_coding_transcript_exon_variant Exon 9 of 10 2
GGNBP2ENST00000619573.1 linkn.1854C>G non_coding_transcript_exon_variant Exon 3 of 6 2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152172
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
30
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152172
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 14, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1169C>G (p.P390R) alteration is located in exon 9 (coding exon 8) of the GGNBP2 gene. This alteration results from a C to G substitution at nucleotide position 1169, causing the proline (P) at amino acid position 390 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Uncertain
0.13
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.040
T
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.63
FATHMM_MKL
Pathogenic
0.99
D
M_CAP
Benign
0.0050
T
MetaRNN
Benign
0.27
T
MetaSVM
Benign
-0.71
T
MutationAssessor
Benign
1.1
L
PrimateAI
Uncertain
0.59
T
Sift4G
Benign
0.082
T
Polyphen
1.0
D
Vest4
0.36
MutPred
0.41
Gain of solvent accessibility (P = 0.0055);
MVP
0.17
ClinPred
0.93
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.14
gMVP
0.15

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1281700307; hg19: chr17-34937922; API