Genetic Variant GGNBP2:p.Phe15Phe (chr17-36545769-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP7BS2

The NM_024835.5(GGNBP2):c.45C>T(p.Phe15Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000758 in 1,583,560 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.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GGNBP2
NM_024835.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.26

Publications

0 publications found

Variant links:

Genes affected

GGNBP2 (HGNC:19357): (gametogenetin binding protein 2) Predicted to be involved in spermatogenesis. Predicted to act upstream of or within several processes, including labyrinthine layer blood vessel development; negative regulation of cell population proliferation; and negative regulation of protein phosphorylation. Predicted to be located in cytoplasmic vesicle. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

GGNBP2 links:

MYO19 (HGNC:26234): (myosin XIX) Enables actin binding activity. Involved in regulation of cytokinesis and regulation of mitochondrial fission. Acts upstream of or within mitochondrion migration along actin filament. Located in cytosol and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

MYO19 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP7

Synonymous conserved (PhyloP=3.26 with no splicing effect.

BS2

High AC in GnomAd4 at 10 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024835.5. 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
	GGNBP2	NM_024835.5	MANE Select	c.45C>T	p.Phe15Phe	synonymous	Exon 2 of 14	NP_079111.1	Q9H3C7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GGNBP2	ENST00000613102.5	TSL:1 MANE Select	c.45C>T	p.Phe15Phe	synonymous	Exon 2 of 14	ENSP00000478220.1	Q9H3C7-1
GGNBP2	ENST00000934644.1		c.45C>T	p.Phe15Phe	synonymous	Exon 1 of 14	ENSP00000604703.1
GGNBP2	ENST00000934643.1		c.45C>T	p.Phe15Phe	synonymous	Exon 2 of 14	ENSP00000604702.1

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000101

AC:

AN:

197724

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000168

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1431488

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

709544

show subpopulations

African (AFR)

AF:

0.0000611

AC:

AN:

32716

American (AMR)

AF:

0.00

AC:

AN:

40370

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25590

East Asian (EAS)

AF:

0.00

AC:

AN:

37598

South Asian (SAS)

AF:

0.00

AC:

AN:

82030

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50690

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1097578

Other (OTH)

AF:

0.00

AC:

AN:

59192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000658

AC:

AN:

152072

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41430

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67992

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

3.3

PromoterAI

-0.048

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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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