chr19-38385557-C-A

Variant names:

• chr19-38385557-C-A
• NM_152657.4:c.1705G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152657.4(GGN):​c.1705G>T​(p.Ala569Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GGN NM_152657.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.896

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]

ENSG00000267090 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08100715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGN	NM_152657.4	c.1705G>T	p.Ala569Ser	missense_variant	Exon 3 of 4	ENST00000334928.11	NP_689870.3
GGN	XM_005258619.5	c.1705G>T	p.Ala569Ser	missense_variant	Exon 3 of 4		XP_005258676.1
GGN	XM_017026451.2	c.1705G>T	p.Ala569Ser	missense_variant	Exon 2 of 3		XP_016881940.1
GGN	XM_011526603.3	c.1456G>T	p.Ala486Ser	missense_variant	Exon 3 of 4		XP_011524905.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GGN	ENST00000334928.11	c.1705G>T	p.Ala569Ser	missense_variant	Exon 3 of 4	1	NM_152657.4	ENSP00000334940.5
GGN	ENST00000591809.5	n.113-57G>T		intron_variant	Intron 2 of 3	1
ENSG00000267090	ENST00000585411.1	n.36C>A		non_coding_transcript_exon_variant	Exon 1 of 2	3
GGN	ENST00000585737.1	n.1367-57G>T		intron_variant	Intron 3 of 4	2		ENSP00000467295.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1705G>T (p.A569S) alteration is located in exon 3 (coding exon 1) of the GGN gene. This alteration results from a G to T substitution at nucleotide position 1705, causing the alanine (A) at amino acid position 569 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.061
Sift	Benign	0.20	T
Sift4G	Uncertain	0.053	T
Polyphen		0.57	P
Vest4		0.23
MutPred		0.10		Gain of phosphorylation at A569 (P = 0.0241);
MVP		0.19
MPC		0.94
ClinPred		0.79	D
GERP RS		0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.073
gMVP		0.093

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.

Other links and lift over

hg19: chr19-38876197;