Genetic Variant ENST00000570780.5:c.969+536A>G (chr17-7312495-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000570780.5(GPS2):c.969+534A>G variant causes a intron 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.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GPS2
ENST00000570780.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.739

Publications

0 publications found

Variant links:

Genes affected

GPS2 (HGNC:4550): (G protein pathway suppressor 2) This gene encodes a protein involved in G protein-mitogen-activated protein kinase (MAPK) signaling cascades. When overexpressed in mammalian cells, this gene could potently suppress a RAS- and MAPK-mediated signal and interfere with JNK activity, suggesting that the function of this gene may be signal repression. The encoded protein is an integral subunit of the NCOR1-HDAC3 (nuclear receptor corepressor 1-histone deacetylase 3) complex, and it was shown that the complex inhibits JNK activation through this subunit and thus could potentially provide an alternative mechanism for hormone-mediated antagonism of AP1 (activator protein 1) function. [provided by RefSeq, Jul 2008]

GPS2 links:

EIF5A (HGNC:3300): (eukaryotic translation initiation factor 5A) Enables U6 snRNA binding activity and protein N-terminus binding activity. Involved in several processes, including cellular response to virus; positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator; and tumor necrosis factor-mediated signaling pathway. Located in annulate lamellae; cytoplasm; and nucleus. Part of nuclear pore. [provided by Alliance of Genome Resources, Apr 2022]

EIF5A Gene-Disease associations (from GenCC):

Faundes-Banka syndrome
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

EIF5A links:

ENSG00000261915 (HGNC:):

ENSG00000261915 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPS2	NM_004489.5 link	c.*261A>G		downstream_gene_variant		ENST00000380728.7	NP_004480.1
EIF5A	NM_001970.5 link	c.*685T>C		downstream_gene_variant		ENST00000336458.13	NP_001961.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein
GPS2	ENST00000380728.7 link	c.*261A>G	downstream_gene_variant	1	NM_004489.5	ENSP00000370104.2
EIF5A	ENST00000336458.13 link	c.*685T>C	downstream_gene_variant	1	NM_001970.5	ENSP00000336776.8
ENSG00000261915	ENST00000575474.1 link	n.*1520A>G	downstream_gene_variant	5		ENSP00000468772.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

297364

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

156150

African (AFR)

AF:

0.00

AC:

AN:

8810

American (AMR)

AF:

0.00

AC:

AN:

11644

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9226

East Asian (EAS)

AF:

0.00

AC:

AN:

19038

South Asian (SAS)

AF:

0.00

AC:

AN:

32718

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20838

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1278

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

176420

Other (OTH)

AF:

0.00

AC:

AN:

17392

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.35

(source)

DANN

Benign

0.60

PhyloP100

-0.74

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over