8-144453385-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001330618.2(ZFTRAF1):​c.448G>A​(p.Ala150Thr) variant causes a missense 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Consequence

ZFTRAF1
NM_001330618.2 missense

Scores

5
10
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.61
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZFTRAF1NM_001330618.2 linkc.448G>A p.Ala150Thr missense_variant 2/4 ENST00000530374.6 NP_001317547.1 P0DTL6-5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZFTRAF1ENST00000530374.6 linkc.448G>A p.Ala150Thr missense_variant 2/43 NM_001330618.2 ENSP00000433769.1 P0DTL6-5
ENSG00000291316ENST00000438911.6 linkc.322G>A p.Ala108Thr missense_variant 3/52 ENSP00000387426.2

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
34

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 16, 2024The c.322G>A (p.A108T) alteration is located in exon 3 (coding exon 3) of the CYHR1 gene. This alteration results from a G to A substitution at nucleotide position 322, causing the alanine (A) at amino acid position 108 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.97
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.040
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.23
T;T;T
Eigen
Uncertain
0.67
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.97
D;D;D
M_CAP
Benign
0.050
D
MetaRNN
Uncertain
0.46
T;T;T
MetaSVM
Benign
-0.56
T
MutationAssessor
Uncertain
2.1
M;.;.
PrimateAI
Pathogenic
0.82
D
PROVEAN
Uncertain
-3.3
D;D;D
REVEL
Uncertain
0.30
Sift
Uncertain
0.0030
D;D;D
Sift4G
Uncertain
0.0050
D;D;.
Polyphen
1.0
D;.;.
Vest4
0.49
MutPred
0.29
Gain of methylation at K104 (P = 0.047);.;.;
MVP
0.73
MPC
0.43
ClinPred
0.97
D
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7
Varity_R
0.50
gMVP
0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1824108874; hg19: chr8-145678768; API