Genetic Variant GGNBP2:p.Gln394Lys (chr17-36581503-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_024835.5(GGNBP2):c.1180C>A(p.Gln394Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000925 in 1,610,326 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000091 ( 0 hom. )

Consequence

GGNBP2
NM_024835.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.83

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]

GGNBP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.037474155).

BS2

High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGNBP2	NM_024835.5 link	c.1180C>A	p.Gln394Lys	missense_variant	Exon 9 of 14	ENST00000613102.5	NP_079111.1	Q9H3C7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GGNBP2	ENST00000613102.5 link	c.1180C>A	p.Gln394Lys	missense_variant	Exon 9 of 14	1	NM_024835.5	ENSP00000478220.1	Q9H3C7-1
GGNBP2	ENST00000617860.4 link	n.2523C>A		non_coding_transcript_exon_variant	Exon 8 of 8	2
GGNBP2	ENST00000618837.4 link	n.1452C>A		non_coding_transcript_exon_variant	Exon 9 of 10	2
GGNBP2	ENST00000619573.1 link	n.1865C>A		non_coding_transcript_exon_variant	Exon 3 of 6	2

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000685

AC:

AN:

248220

Hom.:

AF XY:

0.0000670

AC XY:

AN XY:

134262

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000368

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000532

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000905

AC:

132

AN:

1458184

Hom.:

Cov.:

AF XY:

0.0000799

AC XY:

AN XY:

725486

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000304

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000900

Gnomad4 OTH exome

AF:

0.0000996

GnomAD4 genome

AF:

0.000112

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000988

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 16, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1180C>A (p.Q394K) alteration is located in exon 9 (coding exon 8) of the GGNBP2 gene. This alteration results from a C to A substitution at nucleotide position 1180, causing the glutamine (Q) at amino acid position 394 to be replaced by a lysine (K). 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

0.079

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.018

Eigen

Benign

-0.24

Eigen_PC

Benign

0.0072

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.0018

MetaRNN

Benign

0.037

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.47

Sift4G

Benign

0.94

Polyphen

0.10

Vest4

0.15

MVP

0.043

ClinPred

0.049

GERP RS

5.7

Varity_R

0.15

gMVP

0.22

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over