rs2143009613

Variant names:

• chr17-7311404-C-G
• rs2143009613
• NM_001970.5:c.325C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-7311404-C-G
• chr17-7311404-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PP2 PP3 PP5

The NM_001970.5(EIF5A):​c.325C>G​(p.Arg109Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EIF5A NM_001970.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.50
• Publications: 1 publications found

Genes affected

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]

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 4 curated pathogenic missense variants (we use a threshold of 10). The gene has 1 curated benign missense variants. Gene score misZ: 2.407 (below the threshold of 3.09). Trascript score misZ: 4.4819 (above the threshold of 3.09). GenCC associations: The gene is linked to Faundes-Banka syndrome.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.795
• PP5: Variant 17-7311404-C-G is Pathogenic according to our data. Variant chr17-7311404-C-G is described in ClinVar as Pathogenic. ClinVar VariationId is 1164079.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001970.5. 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
	EIF5A	NM_001970.5	MANE Select	c.325C>G	p.Arg109Gly	missense	Exon 4 of 6	NP_001961.1	P63241-1
	EIF5A	NM_001143760.1		c.415C>G	p.Arg139Gly	missense	Exon 4 of 6	NP_001137232.1	P63241-2
	EIF5A	NM_001143761.1		c.325C>G	p.Arg109Gly	missense	Exon 4 of 6	NP_001137233.1	P63241-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF5A	ENST00000336458.13	TSL:1 MANE Select	c.325C>G	p.Arg109Gly	missense	Exon 4 of 6	ENSP00000336776.8	P63241-1
	EIF5A	ENST00000336452.11	TSL:1	c.415C>G	p.Arg139Gly	missense	Exon 4 of 6	ENSP00000336702.7	P63241-2
	EIF5A	ENST00000416016.2	TSL:1	c.325C>G	p.Arg109Gly	missense	Exon 4 of 6	ENSP00000396073.2	P63241-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Faundes-Banka syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.68	D
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.060	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		3.5
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.73
MutPred		0.63		Gain of glycosylation at S105 (P = 0.0606)
MVP		0.83
MPC		3.5
ClinPred		1.0	D
GERP RS		3.4
Varity_R		0.94
gMVP		0.96

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

Other links and lift over

dbSNP: rs2143009613; hg19: chr17-7214723;