chr17-7312495-T-C

Variant names:

• chr17-7312495-T-C
• ENST00000570780.5:c.969+534A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.739
• Publications: 0 publications found

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]

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

ENSG00000261915 (HGNC:):

ACMG classification

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000570780.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPS2	NM_004489.5	MANE Select	c.*261A>G		downstream_gene	N/A	NP_004480.1
	EIF5A	NM_001970.5	MANE Select	c.*685T>C		downstream_gene	N/A	NP_001961.1
	EIF5A	NM_001143760.1		c.*685T>C		downstream_gene	N/A	NP_001137232.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPS2	ENST00000570780.5	TSL:5	c.969+534A>G		intron	N/A	ENSP00000460836.1
	GPS2	ENST00000380728.7	TSL:1 MANE Select	c.*261A>G		downstream_gene	N/A	ENSP00000370104.2
	EIF5A	ENST00000336458.13	TSL:1 MANE Select	c.*685T>C		downstream_gene	N/A	ENSP00000336776.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 297364 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 156150

African (AFR) AF: 0.00 AC: 0 AN: 8810

American (AMR) AF: 0.00 AC: 0 AN: 11644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9226

East Asian (EAS) AF: 0.00 AC: 0 AN: 19038

South Asian (SAS) AF: 0.00 AC: 0 AN: 32718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1278

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 176420

Other (OTH) AF: 0.00 AC: 0 AN: 17392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.35
DANN	Benign	0.60
PhyloP100		-0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr17-7215814;