8-144450430-CAG-C

Position:

• chr8-144450430-CAG-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001330618.2(ZFTRAF1):​c.1162_1163delCT​(p.Leu388fs) 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 (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZFTRAF1 NM_001330618.2 frameshift
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.08

Genes affected

ZFTRAF1 (HGNC:17806): (zinc finger TRAF-type containing 1) Predicted to enable zinc ion binding activity. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000291316 (HGNC:56752): (TMEM276-ZFTRAF1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring LOC84773 and cysteine and histidine rich 1 (CYHR1). It encodes a fusion protein that shares sequence identity with proteins encoded by both independent genes. [provided by RefSeq, Feb 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 8-144450430-CAG-C is Pathogenic according to our data. Variant chr8-144450430-CAG-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2446709.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFTRAF1	NM_001330618.2	c.1162_1163delCT	p.Leu388fs	frameshift_variant	4/4	ENST00000530374.6	NP_001317547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFTRAF1	ENST00000530374.6	c.1162_1163delCT	p.Leu388fs	frameshift_variant	4/4	3	NM_001330618.2	ENSP00000433769.1
ENSG00000291316	ENST00000438911.6	c.1036_1037delCT	p.Leu346fs	frameshift_variant	5/5	2		ENSP00000387426.2
ZFTRAF1	ENST00000528663.1	n.4971_4972delCT		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Neurodevelopmental disorder with hypotonia and gross motor and speech delay Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

Cologne Center for Genomics, Faculty of Medicine, University of Cologne

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-145675813;