17-49298828-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001145365.3(ZNF652):​c.1406A>G​(p.Tyr469Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

ZNF652
NM_001145365.3 missense

Scores

9
7
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.01
Variant links:
Genes affected
ZNF652 (HGNC:29147): (zinc finger protein 652) Predicted to enable DNA-binding transcription factor 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 Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.853

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF652NM_001145365.3 linkuse as main transcriptc.1406A>G p.Tyr469Cys missense_variant 6/6 ENST00000430262.3 NP_001138837.1 Q9Y2D9A8K9F2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF652ENST00000430262.3 linkuse as main transcriptc.1406A>G p.Tyr469Cys missense_variant 6/61 NM_001145365.3 ENSP00000416305.2 Q9Y2D9
ZNF652ENST00000362063.6 linkuse as main transcriptc.1406A>G p.Tyr469Cys missense_variant 6/61 ENSP00000354686.2 Q9Y2D9
ZNF652ENST00000508237.5 linkuse as main transcriptn.866A>G non_coding_transcript_exon_variant 7/82 ENSP00000424848.1 D6RF85
FLJ40194ENST00000655089.1 linkuse as main transcriptn.863+8332T>C intron_variant

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
31

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 GeneticsMay 15, 2024The c.1406A>G (p.Y469C) alteration is located in exon 6 (coding exon 5) of the ZNF652 gene. This alteration results from a A to G substitution at nucleotide position 1406, causing the tyrosine (Y) at amino acid position 469 to be replaced by a cysteine (C). 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
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.29
T;T
Eigen
Pathogenic
0.70
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.95
.;D
M_CAP
Uncertain
0.10
D
MetaRNN
Pathogenic
0.85
D;D
MetaSVM
Benign
-0.80
T
MutationAssessor
Uncertain
2.7
M;M
PrimateAI
Pathogenic
0.94
D
PROVEAN
Pathogenic
-7.5
D;D
REVEL
Uncertain
0.57
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0010
D;D
Polyphen
1.0
D;D
Vest4
0.77
MutPred
0.65
Gain of disorder (P = 0.0286);Gain of disorder (P = 0.0286);
MVP
0.50
MPC
1.3
ClinPred
1.0
D
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.84
gMVP
0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-47376190; API