chr16-31061817-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_024706.5(ZNF668):c.1111C>T(p.Arg371Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000066 in 151,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ZNF668
NM_024706.5 stop_gained
NM_024706.5 stop_gained
Scores
3
3
1
Clinical Significance
Conservation
PhyloP100: 3.94
Genes affected
ZNF668 (HGNC:25821): (zinc finger protein 668) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.403 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 16-31061817-G-A is Pathogenic according to our data. Variant chr16-31061817-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 1184622.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF668 | NM_024706.5 | c.1111C>T | p.Arg371Ter | stop_gained | 3/3 | ENST00000300849.5 | |
ZNF668 | NM_001172669.2 | c.1180C>T | p.Arg394Ter | stop_gained | 4/4 | ||
ZNF668 | NM_001172668.2 | c.1111C>T | p.Arg371Ter | stop_gained | 3/3 | ||
ZNF668 | NM_001172670.2 | c.1111C>T | p.Arg371Ter | stop_gained | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF668 | ENST00000300849.5 | c.1111C>T | p.Arg371Ter | stop_gained | 3/3 | 1 | NM_024706.5 | P1 | |
ENST00000622229.1 | n.2394G>A | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000660 AC: 1AN: 151494Hom.: 0 Cov.: 32
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1460584Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726656
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GnomAD4 genome ? AF: 0.00000660 AC: 1AN: 151494Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 73962
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Neurodevelopmental disorder with poor growth, large ears, and dysmorphic facies Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 10, 2023 | - - |
Progressive microcephaly;C2315100:Failure to thrive;C3553450:Profound global developmental delay;na:marked facial dysmorphism Pathogenic:1
Pathogenic, no assertion criteria provided | research | Department Of Translational Genomics (developmental Genetics Section), King Faisal Specialist Hospital & Research Centre | Jul 15, 2021 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
D;D;D;D;D;D
Vest4
ClinPred
D
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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