Variant chr19-38384432-G-A details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.65

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]

GGN links:

Genome browser will be placed here

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
GGN	NM_152657.4 linkuse as main transcript	c.1939C>T	p.Gln647Ter	stop_gained	4/4	ENST00000334928.11
GGN	XM_005258619.5 linkuse as main transcript	c.1939C>T	p.Gln647Ter	stop_gained	4/4
GGN	XM_017026451.2 linkuse as main transcript	c.1939C>T	p.Gln647Ter	stop_gained	3/3
GGN	XM_011526603.3 linkuse as main transcript	c.1690C>T	p.Gln564Ter	stop_gained	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GGN	ENST00000334928.11 linkuse as main transcript	c.1939C>T	p.Gln647Ter	stop_gained	4/4	1	NM_152657.4	P1	Q86UU5-1
GGN	ENST00000591809.5 linkuse as main transcript	n.290C>T		non_coding_transcript_exon_variant	4/4	1
GGN	ENST00000585737.1 linkuse as main transcript	c.*170C>T		3_prime_UTR_variant, NMD_transcript_variant	5/5	2			Q86UU5-2

Frequencies

GnomAD3 genomes

AF:

0.00790

AC:

1202

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00766

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00372

Gnomad FIN

AF:

0.00678

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0124

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00815

AC:

2048

AN:

251244

Hom.:

AF XY:

0.00846

AC XY:

1149

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.00240

Gnomad AMR exome

AF:

0.00533

Gnomad ASJ exome

AF:

0.00775

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00484

Gnomad FIN exome

AF:

0.00710

Gnomad NFE exome

AF:

0.0122

Gnomad OTH exome

AF:

0.00978

GnomAD4 exome

AF:

0.0118

AC:

17295

AN:

1461206

Hom.:

134

Cov.:

AF XY:

0.0117

AC XY:

8506

AN XY:

726938

show subpopulations

Gnomad4 AFR exome

AF:

0.00179

Gnomad4 AMR exome

AF:

0.00570

Gnomad4 ASJ exome

AF:

0.00766

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00509

Gnomad4 FIN exome

AF:

0.00630

Gnomad4 NFE exome

AF:

0.0138

Gnomad4 OTH exome

AF:

0.0108

GnomAD4 genome

AF:

0.00789

AC:

1201

AN:

152310

Hom.:

Cov.:

AF XY:

0.00764

AC XY:

569

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00241

Gnomad4 AMR

AF:

0.00765

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00678

Gnomad4 NFE

AF:

0.0124

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00584

Hom.:

Bravo

AF:

0.00786

TwinsUK

AF:

0.0143

AC:

ALSPAC

AF:

0.0158

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0124

AC:

107

ExAC

AF:

0.00802

AC:

974

EpiCase

AF:

0.0145

EpiControl

AF:

0.0143

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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Pathogenic

0.49

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Uncertain

0.91

MutationTaster

Benign

1.0

Vest4

0.68

GERP RS

4.6

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.

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