8-144452428-G-A

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

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.64
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 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

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZFTRAF1NM_001330618.2 linkc.754C>T p.His252Tyr missense_variant 3/4 ENST00000530374.6 NP_001317547.1 P0DTL6-5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZFTRAF1ENST00000530374.6 linkc.754C>T p.His252Tyr missense_variant 3/43 NM_001330618.2 ENSP00000433769.1 P0DTL6-5
ENSG00000291316ENST00000438911.6 linkc.628C>T p.His210Tyr missense_variant 4/52 ENSP00000387426.2

Frequencies

GnomAD3 genomes
AF:
0.000210
AC:
32
AN:
152204
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.000748
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000514
AC:
8
AN:
155582
Hom.:
0
AF XY:
0.0000242
AC XY:
2
AN XY:
82556
show subpopulations
Gnomad AFR exome
AF:
0.000882
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000166
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000179
AC:
25
AN:
1397760
Hom.:
0
Cov.:
31
AF XY:
0.0000160
AC XY:
11
AN XY:
689472
show subpopulations
Gnomad4 AFR exome
AF:
0.000475
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:
0.00000834
Gnomad4 OTH exome
AF:
0.0000172
GnomAD4 genome
AF:
0.000210
AC:
32
AN:
152322
Hom.:
0
Cov.:
34
AF XY:
0.000215
AC XY:
16
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.000746
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000194
Hom.:
0
Bravo
AF:
0.000147

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 GeneticsMar 06, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.051
T;T;T
Eigen
Benign
-0.049
Eigen_PC
Benign
0.14
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.89
D;D;D
M_CAP
Benign
0.0077
T
MetaRNN
Benign
0.039
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;.;.
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-1.6
N;N;N
REVEL
Benign
0.086
Sift
Benign
0.78
T;T;T
Sift4G
Benign
1.0
T;T;.
Polyphen
0.17
B;.;.
Vest4
0.33
MVP
0.21
MPC
0.12
ClinPred
0.065
T
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.21
gMVP
0.98

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: rs536889577; hg19: chr8-145677811; API