19-43997337-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198089.3(ZNF155):ā€‹c.1480G>Cā€‹(p.Val494Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

ZNF155
NM_198089.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.70
Variant links:
Genes affected
ZNF155 (HGNC:12940): (zinc finger protein 155) 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]
ZNF230-DT (HGNC:55316): (ZNF230 divergent transcript)

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=0.061741203).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF155NM_198089.3 linkuse as main transcriptc.1480G>C p.Val494Leu missense_variant 5/5 ENST00000270014.7
ZNF230-DTNR_110727.1 linkuse as main transcriptn.1775C>G non_coding_transcript_exon_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF155ENST00000270014.7 linkuse as main transcriptc.1480G>C p.Val494Leu missense_variant 5/51 NM_198089.3 P2Q12901-1
ZNF230-DTENST00000586860.1 linkuse as main transcriptn.2109C>G non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461554
Hom.:
0
Cov.:
79
AF XY:
0.00000138
AC XY:
1
AN XY:
727076
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 23, 2023The c.1480G>C (p.V494L) alteration is located in exon 5 (coding exon 4) of the ZNF155 gene. This alteration results from a G to C substitution at nucleotide position 1480, causing the valine (V) at amino acid position 494 to be replaced by a leucine (L). 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
0.14
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
0.23
DANN
Benign
0.89
DEOGEN2
Benign
0.0041
T;.;T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.011
N
LIST_S2
Benign
0.049
T;T;.;.
M_CAP
Benign
0.0013
T
MetaRNN
Benign
0.062
T;T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.78
N;.;N;N
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.63
.;N;N;.
REVEL
Benign
0.040
Sift
Uncertain
0.021
.;D;D;.
Sift4G
Benign
0.24
T;T;T;T
Polyphen
0.24
B;.;B;B
Vest4
0.076
MutPred
0.30
Loss of MoRF binding (P = 0.0982);.;Loss of MoRF binding (P = 0.0982);Loss of MoRF binding (P = 0.0982);
MVP
0.092
MPC
0.075
ClinPred
0.14
T
GERP RS
-0.73
Varity_R
0.066
gMVP
0.012

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: chr19-44501489; API