NM_001970.5:c.191_192delTT

Variant names:

• chr17-7311041-CTT-C
• NM_001970.5:c.191_192delTT

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001970.5(EIF5A):​c.191_192delTT​(p.Phe64TyrfsTer6) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EIF5A NM_001970.5 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 7.54
• Publications: 0 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]

EIF5A Gene-Disease associations (from GenCC):

• Faundes-Banka syndrome

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

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-7311041-CTT-C is Pathogenic according to our data. Variant chr17-7311041-CTT-C is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 2413190.Status of the report is criteria_provided_single_submitter, 1 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.191_192delTT	p.Phe64TyrfsTer6	frameshift	Exon 3 of 6	NP_001961.1	P63241-1
	EIF5A	NM_001143760.1		c.281_282delTT	p.Phe94TyrfsTer6	frameshift	Exon 3 of 6	NP_001137232.1	P63241-2
	EIF5A	NM_001143761.1		c.191_192delTT	p.Phe64TyrfsTer6	frameshift	Exon 3 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.191_192delTT	p.Phe64TyrfsTer6	frameshift	Exon 3 of 6	ENSP00000336776.8	P63241-1
	EIF5A	ENST00000336452.11	TSL:1	c.281_282delTT	p.Phe94TyrfsTer6	frameshift	Exon 3 of 6	ENSP00000336702.7	P63241-2
	EIF5A	ENST00000416016.2	TSL:1	c.191_192delTT	p.Phe64TyrfsTer6	frameshift	Exon 3 of 6	ENSP00000396073.2	P63241-1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.5

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

hg19: chr17-7214360;