8-144450430-CAG-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

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

Scores

Not classified

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.08
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
ZFTRAF1NM_001330618.2 linkc.1162_1163delCT p.Leu388fs frameshift_variant 4/4 ENST00000530374.6 NP_001317547.1 P0DTL6-5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZFTRAF1ENST00000530374.6 linkc.1162_1163delCT p.Leu388fs frameshift_variant 4/43 NM_001330618.2 ENSP00000433769.1 P0DTL6-5
ENSG00000291316ENST00000438911.6 linkc.1036_1037delCT p.Leu346fs frameshift_variant 5/52 ENSP00000387426.2
ZFTRAF1ENST00000528663.1 linkn.4971_4972delCT non_coding_transcript_exon_variant 3/31

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
LINK: link

Submissions by phenotype

Neurodevelopmental disorder with hypotonia and gross motor and speech delay Pathogenic:1
Likely pathogenic, no assertion criteria providedclinical testingCologne Center for Genomics, Faculty of Medicine, University of Cologne-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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; API