19-38385791-C-T

Variant names:

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

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]

GGN links:

ENSG00000267090 (HGNC:):

ENSG00000267090 links:

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
GGN	NM_152657.4 link	c.1471G>A	p.Asp491Asn	missense_variant	Exon 3 of 4	ENST00000334928.11	NP_689870.3	Q86UU5-1
GGN	XM_005258619.5 link	c.1471G>A	p.Asp491Asn	missense_variant	Exon 3 of 4		XP_005258676.1	Q86UU5-1
GGN	XM_017026451.2 link	c.1471G>A	p.Asp491Asn	missense_variant	Exon 2 of 3		XP_016881940.1	Q86UU5-1
GGN	XM_011526603.3 link	c.1222G>A	p.Asp408Asn	missense_variant	Exon 3 of 4		XP_011524905.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GGN	ENST00000334928.11 link	c.1471G>A	p.Asp491Asn	missense_variant	Exon 3 of 4	1	NM_152657.4	ENSP00000334940.5	Q86UU5-1
GGN	ENST00000591809.5 link	n.113-291G>A		intron_variant	Intron 2 of 3	1
GGN	ENST00000585737.1 link	n.1222G>A		non_coding_transcript_exon_variant	Exon 3 of 5	2		ENSP00000467295.1	Q86UU5-2
ENSG00000267090	ENST00000585411.1 link	n.212+58C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.00193

AC:

293

AN:

152068

Hom.:

Cov.:

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.:

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.:

Cov.:

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.:

Cov.:

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.:

Bravo

AF:

0.00216

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00208

AC:

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

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.43

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.0049

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.8

REVEL

Benign

0.025

Sift

Uncertain

0.029

Sift4G

Benign

0.45

Polyphen

0.045

Vest4

0.15

MVP

0.22

MPC

0.30

ClinPred

0.0058

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.

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