19-38385623-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -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. 11/19 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGN	NM_152657.4 link	c.1639G>A	p.Gly547Ser	missense_variant	Exon 3 of 4	ENST00000334928.11	NP_689870.3	Q86UU5-1
GGN	XM_005258619.5 link	c.1639G>A	p.Gly547Ser	missense_variant	Exon 3 of 4		XP_005258676.1	Q86UU5-1
GGN	XM_017026451.2 link	c.1639G>A	p.Gly547Ser	missense_variant	Exon 2 of 3		XP_016881940.1	Q86UU5-1
GGN	XM_011526603.3 link	c.1390G>A	p.Gly464Ser	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>A	p.Gly547Ser	missense_variant	Exon 3 of 4	1	NM_152657.4	ENSP00000334940.5	Q86UU5-1
GGN	ENST00000591809.5 link	n.113-123G>A		intron_variant	Intron 2 of 3	1
ENSG00000267090	ENST00000585411.1 link	n.102C>T		non_coding_transcript_exon_variant	Exon 1 of 2	3
GGN	ENST00000585737.1 link	n.1366+24G>A		intron_variant	Intron 3 of 4	2		ENSP00000467295.1	Q86UU5-2

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

GnomAD3 exomes

AF:

0.00247

AC:

618

AN:

250350

Hom.:

AF XY:

0.00185

AC XY:

251

AN XY:

135580

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 SAS exome

AF:

0.0000653

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

Gnomad4 AFR exome

AF:

0.0316

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.00781

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000755

Gnomad4 OTH exome

AF:

0.00212

GnomAD4 genome

AF:

0.00862

AC:

1313

AN:

152366

Hom.:

Cov.:

AF XY:

0.00874

AC XY:

651

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.0295

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00197

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.32

CADD

Benign

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over