19-38385623-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_152657.4(GGN):c.1639G>A(p.Gly547Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,614,118 control chromosomes in the GnomAD database, including 39 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 Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G547D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0086 ( 21 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 18 hom. )

Consequence

GGN
NM_152657.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.674

Publications

5 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043177903).

BP6

Variant 19-38385623-C-T is Benign according to our data. Variant chr19-38385623-C-T is described in ClinVar as Benign. ClinVar VariationId is 785622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00862 (1313/152366) while in subpopulation AFR AF = 0.0295 (1226/41588). AF 95% confidence interval is 0.0281. There are 21 homozygotes in GnomAd4. There are 651 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 21 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.1639G>A	p.Gly547Ser	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.1639G>A	p.Gly547Ser	missense	Exon 3 of 4	ENSP00000334940.5	Q86UU5-1
GGN	ENST00000591809.5	TSL:1	n.113-123G>A		intron	N/A
GGN	ENST00000904714.1		c.1639G>A	p.Gly547Ser	missense	Exon 3 of 4	ENSP00000574773.1

Frequencies

GnomAD3 genomes

AF:

0.00862

AC:

1312

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0295

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00718

GnomAD2 exomes

AF:

0.00247

AC:

618

AN:

250350

AF XY:

0.00185

show subpopulations

Gnomad AFR exome

AF:

0.0286

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00905

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000160

Gnomad OTH exome

AF:

0.000980

GnomAD4 exome

AF:

0.00105

AC:

1540

AN:

1461752

Hom.:

Cov.:

AF XY:

0.000912

AC XY:

663

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.0316

AC:

1057

AN:

33476

American (AMR)

AF:

0.00127

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00781

AC:

204

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53334

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000755

AC:

AN:

1111980

Other (OTH)

AF:

0.00212

AC:

128

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

102

203

305

406

508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.00862

AC:

1313

AN:

152366

Hom.:

Cov.:

AF XY:

0.00874

AC XY:

651

AN XY:

74512

show subpopulations

African (AFR)

AF:

0.0295

AC:

1226

AN:

41588

American (AMR)

AF:

0.00235

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00806

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68032

Other (OTH)

AF:

0.00710

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

146

219

292

365

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00359

Hom.:

Bravo

AF:

0.00932

ESP6500AA

AF:

0.0300

AC:

132

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00292

AC:

354

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000356

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.021

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0043

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PhyloP100

0.67

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.053

Sift

Pathogenic

0.0

Sift4G

Benign

0.46

Polyphen

0.67

Vest4

0.30

MVP

0.30

MPC

1.0

ClinPred

0.088

GERP RS

2.5

Varity_R

0.43

gMVP

0.34

Mutation Taster

=96/4

polymorphism

(source)

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

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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