19-38385791-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_152657.4(GGN):​c.1471G>A​(p.Asp491Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00232 in 1,548,736 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0024 ( 8 hom. )

Consequence

GGN
NM_152657.4 missense

Scores

4
15

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0300
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0048636794).
BP6
Variant 19-38385791-C-T is Benign according to our data. Variant chr19-38385791-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 708829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GGNNM_152657.4 linkc.1471G>A p.Asp491Asn missense_variant Exon 3 of 4 ENST00000334928.11 NP_689870.3 Q86UU5-1
GGNXM_005258619.5 linkc.1471G>A p.Asp491Asn missense_variant Exon 3 of 4 XP_005258676.1 Q86UU5-1
GGNXM_017026451.2 linkc.1471G>A p.Asp491Asn missense_variant Exon 2 of 3 XP_016881940.1 Q86UU5-1
GGNXM_011526603.3 linkc.1222G>A p.Asp408Asn missense_variant Exon 3 of 4 XP_011524905.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GGNENST00000334928.11 linkc.1471G>A p.Asp491Asn missense_variant Exon 3 of 4 1 NM_152657.4 ENSP00000334940.5 Q86UU5-1
GGNENST00000591809.5 linkn.113-291G>A intron_variant Intron 2 of 3 1
GGNENST00000585737.1 linkn.1222G>A non_coding_transcript_exon_variant Exon 3 of 5 2 ENSP00000467295.1 Q86UU5-2
ENSG00000267090ENST00000585411.1 linkn.212+58C>T intron_variant Intron 1 of 1 3

Frequencies

GnomAD3 genomes
AF:
0.00193
AC:
293
AN:
152068
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000579
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00557
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.0000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00259
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00175
AC:
262
AN:
149606
Hom.:
1
AF XY:
0.00182
AC XY:
151
AN XY:
83012
show subpopulations
Gnomad AFR exome
AF:
0.000263
Gnomad AMR exome
AF:
0.00350
Gnomad ASJ exome
AF:
0.00134
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000632
Gnomad FIN exome
AF:
0.000108
Gnomad NFE exome
AF:
0.00232
Gnomad OTH exome
AF:
0.00143
GnomAD4 exome
AF:
0.00237
AC:
3306
AN:
1396554
Hom.:
8
Cov.:
34
AF XY:
0.00226
AC XY:
1559
AN XY:
690742
show subpopulations
Gnomad4 AFR exome
AF:
0.000596
Gnomad4 AMR exome
AF:
0.00327
Gnomad4 ASJ exome
AF:
0.000815
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000594
Gnomad4 FIN exome
AF:
0.0000504
Gnomad4 NFE exome
AF:
0.00271
Gnomad4 OTH exome
AF:
0.00229
GnomAD4 genome
AF:
0.00193
AC:
293
AN:
152182
Hom.:
0
Cov.:
33
AF XY:
0.00206
AC XY:
153
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.000578
Gnomad4 AMR
AF:
0.00556
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.00259
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.000690
Hom.:
0
Bravo
AF:
0.00216
TwinsUK
AF:
0.00189
AC:
7
ALSPAC
AF:
0.00208
AC:
8
ExAC
AF:
0.00113
AC:
115

ClinVar

Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

GGN-related disorder Benign:1
May 31, 2023
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.59
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.017
T
Eigen
Benign
-0.94
Eigen_PC
Benign
-0.97
FATHMM_MKL
Benign
0.091
N
LIST_S2
Benign
0.43
T
M_CAP
Uncertain
0.17
D
MetaRNN
Benign
0.0049
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
2.0
M
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-1.8
N
REVEL
Benign
0.025
Sift
Uncertain
0.029
D
Sift4G
Benign
0.45
T
Polyphen
0.045
B
Vest4
0.15
MVP
0.22
MPC
0.30
ClinPred
0.0058
T
GERP RS
0.83
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Varity_R
0.10
gMVP
0.090

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

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

Other links and lift over

dbSNP: rs200124007; hg19: chr19-38876431; COSMIC: COSV53055824; COSMIC: COSV53055824; API