17-36581492-C-T

Variant names:

• chr17-36581492-C-T
• rs1281700307
• NM_024835.5:c.1169C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024835.5(GGNBP2):​c.1169C>T​(p.Pro390Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,262 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. P390R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GGNBP2 NM_024835.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.79
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24671048).

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.1169C>T	p.Pro390Leu	missense	Exon 9 of 14	NP_079111.1	Q9H3C7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGNBP2	ENST00000613102.5	TSL:1 MANE Select	c.1169C>T	p.Pro390Leu	missense	Exon 9 of 14	ENSP00000478220.1	Q9H3C7-1
	GGNBP2	ENST00000934644.1		c.1298C>T	p.Pro433Leu	missense	Exon 9 of 14	ENSP00000604703.1
	GGNBP2	ENST00000934643.1		c.1175C>T	p.Pro392Leu	missense	Exon 9 of 14	ENSP00000604702.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459262 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725888

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33288

American (AMR) AF: 0.00 AC: 0 AN: 44040

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111176

Other (OTH) AF: 0.00 AC: 0 AN: 60304

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.067	T
Eigen	Uncertain	0.62
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	1.1	L
PhyloP100		6.8
PrimateAI	Uncertain	0.59	T
Sift4G	Uncertain	0.058	T
Polyphen		1.0	D
Vest4		0.27
MutPred		0.40		Loss of glycosylation at T391 (P = 0.0648)
MVP		0.13
ClinPred		0.95	D
GERP RS		5.7
Varity_R		0.16
gMVP		0.21

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

Other links and lift over

dbSNP: rs1281700307; hg19: chr17-34937922;