8-144452428-G-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001330618.2(ZFTRAF1):c.754C>T(p.His252Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000368 in 1,550,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00021 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
ZFTRAF1
NM_001330618.2 missense
NM_001330618.2 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 5.64
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 Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03878978).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000210 AC: 32AN: 152204Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000514 AC: 8AN: 155582Hom.: 0 AF XY: 0.0000242 AC XY: 2AN XY: 82556
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GnomAD4 exome AF: 0.0000179 AC: 25AN: 1397760Hom.: 0 Cov.: 31 AF XY: 0.0000160 AC XY: 11AN XY: 689472
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GnomAD4 genome AF: 0.000210 AC: 32AN: 152322Hom.: 0 Cov.: 34 AF XY: 0.000215 AC XY: 16AN XY: 74466
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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 submitter | clinical testing | Ambry Genetics | Mar 06, 2023 | The c.628C>T (p.H210Y) alteration is located in exon 4 (coding exon 4) of the CYHR1 gene. This alteration results from a C to T substitution at nucleotide position 628, causing the histidine (H) at amino acid position 210 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;.
Polyphen
B;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at