rs147254848

Variant names:

• chr19-38385436-C-A
• rs147254848
• NM_152657.4:c.1826G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-38385436-C-A
• chr19-38385436-C-G
• chr19-38385436-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152657.4(GGN):​c.1826G>T​(p.Arg609Leu) 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. 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. R609H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GGN NM_152657.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37869567).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGN	NM_152657.4	c.1826G>T	p.Arg609Leu	missense_variant	Exon 3 of 4	ENST00000334928.11	NP_689870.3
GGN	XM_005258619.5	c.1826G>T	p.Arg609Leu	missense_variant	Exon 3 of 4		XP_005258676.1
GGN	XM_017026451.2	c.1826G>T	p.Arg609Leu	missense_variant	Exon 2 of 3		XP_016881940.1
GGN	XM_011526603.3	c.1577G>T	p.Arg526Leu	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.1826G>T	p.Arg609Leu	missense_variant	Exon 3 of 4	1	NM_152657.4	ENSP00000334940.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.56	T
M_CAP	Uncertain	0.090	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	0.97	L
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.091
Sift	Uncertain	0.0080	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.48
MutPred		0.30		Loss of MoRF binding (P = 0.0059);
MVP		0.61
MPC		1.1
ClinPred		0.98	D
GERP RS		3.6
Varity_R		0.26
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs147254848; hg19: chr19-38876076;