8-144453351-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001330618.2(ZFTRAF1):ā€‹c.482A>Gā€‹(p.Lys161Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000429 in 1,398,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 34)
Exomes š‘“: 0.0000043 ( 0 hom. )

Consequence

ZFTRAF1
NM_001330618.2 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.88
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1620583).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZFTRAF1NM_001330618.2 linkc.482A>G p.Lys161Arg 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.482A>G p.Lys161Arg missense_variant 2/43 NM_001330618.2 ENSP00000433769.1 P0DTL6-5
ENSG00000291316ENST00000438911.6 linkc.356A>G p.Lys119Arg missense_variant 3/52 ENSP00000387426.2

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
0.00000429
AC:
6
AN:
1398814
Hom.:
0
Cov.:
31
AF XY:
0.00000580
AC XY:
4
AN XY:
689892
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000556
Gnomad4 OTH exome
AF:
0.00
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 GeneticsOct 06, 2024The c.356A>G (p.K119R) alteration is located in exon 3 (coding exon 3) of the CYHR1 gene. This alteration results from a A to G substitution at nucleotide position 356, causing the lysine (K) at amino acid position 119 to be replaced by an arginine (R). 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
Benign
0.12
BayesDel_addAF
Benign
-0.066
T
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.050
T;T;T
Eigen
Benign
-0.046
Eigen_PC
Benign
0.18
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.16
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;.;.
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-1.1
N;N;N
REVEL
Benign
0.092
Sift
Benign
0.39
T;T;T
Sift4G
Benign
0.28
T;T;.
Polyphen
0.0090
B;.;.
Vest4
0.28
MutPred
0.29
Loss of methylation at K119 (P = 0.0149);.;.;
MVP
0.35
MPC
0.084
ClinPred
0.42
T
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7
Varity_R
0.13
gMVP
0.43

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs1824107681; hg19: chr8-145678734; API