17-36554862-C-T

Variant names:

• chr17-36554862-C-T
• rs1272049948
• NM_024835.5:c.136C>T

Variant summary

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

The NM_024835.5(GGNBP2):​c.136C>T​(p.His46Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: GGNBP2 NM_024835.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.64

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

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=0.13107899).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGNBP2	NM_024835.5	c.136C>T	p.His46Tyr	missense_variant	Exon 3 of 14	ENST00000613102.5	NP_079111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GGNBP2	ENST00000613102.5	c.136C>T	p.His46Tyr	missense_variant	Exon 3 of 14	1	NM_024835.5	ENSP00000478220.1
GGNBP2	ENST00000616019.1	c.136C>T	p.His46Tyr	missense_variant	Exon 2 of 4	2		ENSP00000484094.1
GGNBP2	ENST00000617860.4	n.421C>T		non_coding_transcript_exon_variant	Exon 3 of 8	2
GGNBP2	ENST00000618837.4	n.408C>T		non_coding_transcript_exon_variant	Exon 3 of 10	2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152118 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 27

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152118 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74290

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.136C>T (p.H46Y) alteration is located in exon 3 (coding exon 2) of the GGNBP2 gene. This alteration results from a C to T substitution at nucleotide position 136, causing the histidine (H) at amino acid position 46 to be replaced by a tyrosine (Y). 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	0.082
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Benign	0.72
DEOGEN2	Benign	0.044	T;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.025
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.55	N;.
PrimateAI	Uncertain	0.73	T
Sift4G	Benign	1.0	T;T
Polyphen		0.0040	B;.
Vest4		0.18
MutPred		0.26		Loss of disorder (P = 0.0497);Loss of disorder (P = 0.0497);
MVP		0.043
ClinPred		0.68	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.57

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

LitVar

Other links and lift over

dbSNP: rs1272049948; hg19: chr17-34910703;