1-85706305-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_017953.4(ZNHIT6):c.773G>A(p.Arg258Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000645 in 1,613,274 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000040 ( 0 hom. )
Consequence
ZNHIT6
NM_017953.4 missense
NM_017953.4 missense
Scores
6
9
4
Clinical Significance
Conservation
PhyloP100: 6.32
Genes affected
ZNHIT6 (HGNC:26089): (zinc finger HIT-type containing 6) Enables ATPase binding activity; TFIID-class transcription factor complex binding activity; and identical protein binding activity. Involved in box C/D snoRNP assembly; protein complex oligomerization; and snoRNA localization. Located in extracellular exosome. Part of pre-snoRNP complex. [provided by Alliance of Genome Resources, Apr 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
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000302 AC: 46AN: 152152Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000100 AC: 25AN: 249918Hom.: 0 AF XY: 0.0000666 AC XY: 9AN XY: 135052
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GnomAD4 exome AF: 0.0000397 AC: 58AN: 1461004Hom.: 0 Cov.: 32 AF XY: 0.0000344 AC XY: 25AN XY: 726718
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GnomAD4 genome AF: 0.000302 AC: 46AN: 152270Hom.: 0 Cov.: 32 AF XY: 0.000255 AC XY: 19AN XY: 74440
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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 | May 16, 2024 | The c.773G>A (p.R258Q) alteration is located in exon 3 (coding exon 3) of the ZNHIT6 gene. This alteration results from a G to A substitution at nucleotide position 773, causing the arginine (R) at amino acid position 258 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
.;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
.;M
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
T;T
Polyphen
1.0
.;D
Vest4
MVP
MPC
0.74
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