chr19-38385791-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

spermatogenic failure 69
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

GGN links:

ENSG00000267090 (HGNC:):

ENSG00000267090 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 708829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152657.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGN	NM_152657.4	MANE Select	c.1471G>A	p.Asp491Asn	missense	Exon 3 of 4	NP_689870.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GGN	ENST00000334928.11	TSL:1 MANE Select	c.1471G>A	p.Asp491Asn	missense	Exon 3 of 4	ENSP00000334940.5	Q86UU5-1
GGN	ENST00000591809.5	TSL:1	n.113-291G>A		intron	N/A
GGN	ENST00000904714.1		c.1471G>A	p.Asp491Asn	missense	Exon 3 of 4	ENSP00000574773.1

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

GnomAD2 exomes

AF:

0.00175

AC:

262

AN:

149606

AF XY:

0.00182

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 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

African (AFR)

AF:

0.000596

AC:

AN:

31896

American (AMR)

AF:

0.00327

AC:

117

AN:

35814

Ashkenazi Jewish (ASJ)

AF:

0.000815

AC:

AN:

24530

East Asian (EAS)

AF:

0.00

AC:

AN:

36526

South Asian (SAS)

AF:

0.000594

AC:

AN:

80826

European-Finnish (FIN)

AF:

0.0000504

AC:

AN:

39644

Middle Eastern (MID)

AF:

0.00486

AC:

AN:

5142

European-Non Finnish (NFE)

AF:

0.00271

AC:

2942

AN:

1084146

Other (OTH)

AF:

0.00229

AC:

133

AN:

58030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

162

324

486

648

810

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

118

236

354

472

590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00193

AC:

293

AN:

152182

Hom.:

Cov.:

AF XY:

0.00206

AC XY:

153

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.000578

AC:

AN:

41538

American (AMR)

AF:

0.00556

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00259

AC:

176

AN:

67980

Other (OTH)

AF:

0.00237

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

GGN-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

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

PhyloP100

0.030

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

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over