Genetic Variant GGN:p.Asp491Tyr (chr19-38385791-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152657.4(GGN):c.1471G>T(p.Asp491Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000043 in 1,396,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D491N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

GGN
NM_152657.4 missense

Scores

Clinical Significance

Not reported in ClinVar

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24755663).

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>T	p.Asp491Tyr	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>T	p.Asp491Tyr	missense	Exon 3 of 4	ENSP00000334940.5	Q86UU5-1
GGN	ENST00000591809.5	TSL:1	n.113-291G>T		intron	N/A
GGN	ENST00000904714.1		c.1471G>T	p.Asp491Tyr	missense	Exon 3 of 4	ENSP00000574773.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000668

AC:

AN:

149606

AF XY:

0.0000120

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000163

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000430

AC:

AN:

1396558

Hom.:

Cov.:

AF XY:

0.00000869

AC XY:

AN XY:

690742

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31896

American (AMR)

AF:

0.00

AC:

AN:

35814

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24530

East Asian (EAS)

AF:

0.00

AC:

AN:

36526

South Asian (SAS)

AF:

0.00

AC:

AN:

80826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39644

Middle Eastern (MID)

AF:

0.000194

AC:

AN:

5142

European-Non Finnish (NFE)

AF:

0.00000369

AC:

AN:

1084150

Other (OTH)

AF:

0.0000172

AC:

AN:

58030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.12

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.39

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PhyloP100

0.030

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.064

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.049

Polyphen

0.99

Vest4

0.23

MutPred

0.15

Gain of phosphorylation at D491 (P = 0.0227)

MVP

0.29

MPC

0.38

ClinPred

0.87

GERP RS

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.31

gMVP

0.26

Mutation Taster

=96/4

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over