dbSNP rs79261673: GGN:p.Gly547Arg (chr19-38385623-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_152657.4(GGN):c.1639G>C(p.Gly547Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. G547S) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GGN
NM_152657.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.674

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3796353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGN	NM_152657.4 link	c.1639G>C	p.Gly547Arg	missense_variant	Exon 3 of 4	ENST00000334928.11	NP_689870.3	Q86UU5-1
GGN	XM_005258619.5 link	c.1639G>C	p.Gly547Arg	missense_variant	Exon 3 of 4		XP_005258676.1	Q86UU5-1
GGN	XM_017026451.2 link	c.1639G>C	p.Gly547Arg	missense_variant	Exon 2 of 3		XP_016881940.1	Q86UU5-1
GGN	XM_011526603.3 link	c.1390G>C	p.Gly464Arg	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.1639G>C	p.Gly547Arg	missense_variant	Exon 3 of 4	1	NM_152657.4	ENSP00000334940.5	Q86UU5-1
GGN	ENST00000591809.5 link	n.113-123G>C		intron_variant	Intron 2 of 3	1
ENSG00000267090	ENST00000585411.1 link	n.102C>G		non_coding_transcript_exon_variant	Exon 1 of 2	3
GGN	ENST00000585737.1 link	n.1366+24G>C		intron_variant	Intron 3 of 4	2		ENSP00000467295.1	Q86UU5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461752

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.63

M_CAP

Benign

0.077

MetaRNN

Benign

0.38

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.13

Sift

Pathogenic

0.0

Sift4G

Benign

0.20

Polyphen

1.0

Vest4

0.50

MutPred

0.28

Gain of MoRF binding (P = 0.0174);

MVP

0.41

MPC

1.1

ClinPred

0.99

GERP RS

2.5

Varity_R

0.40

gMVP

0.34

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over