10-43609333-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145312.4(ZNF485):​c.230C>T​(p.Pro77Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,613,722 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 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

ZNF485
NM_145312.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.107
Variant links:
Genes affected
ZNF485 (HGNC:23440): (zinc finger protein 485) 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09486535).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF485NM_145312.4 linkc.230C>T p.Pro77Leu missense_variant Exon 4 of 5 ENST00000361807.8 NP_660355.2 Q8NCK3-1A0A024R7T5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF485ENST00000361807.8 linkc.230C>T p.Pro77Leu missense_variant Exon 4 of 5 1 NM_145312.4 ENSP00000354694.3 Q8NCK3-1
ZNF485ENST00000374435.3 linkc.230C>T p.Pro77Leu missense_variant Exon 4 of 5 1 ENSP00000363558.3 Q8NCK3-1
ZNF485ENST00000430885.5 linkc.230C>T p.Pro77Leu missense_variant Exon 4 of 5 2 ENSP00000393570.1 C9JV60

Frequencies

GnomAD3 genomes
AF:
0.0000986
AC:
15
AN:
152186
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000338
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:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
250584
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135578
show subpopulations
Gnomad AFR exome
AF:
0.000248
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:
0.00000884
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.0000349
AC:
51
AN:
1461536
Hom.:
0
Cov.:
30
AF XY:
0.0000206
AC XY:
15
AN XY:
727084
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000351
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000986
AC:
15
AN:
152186
Hom.:
0
Cov.:
32
AF XY:
0.0000942
AC XY:
7
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.000338
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:
0.00
Gnomad4 OTH
AF:
0.000478
Bravo
AF:
0.000125
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000494
AC:
6

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.230C>T (p.P77L) alteration is located in exon 4 (coding exon 3) of the ZNF485 gene. This alteration results from a C to T substitution at nucleotide position 230, causing the proline (P) at amino acid position 77 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
0.088
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
7.0
DANN
Uncertain
0.98
DEOGEN2
Benign
0.014
T;T;T
Eigen
Benign
-0.63
Eigen_PC
Benign
-0.74
FATHMM_MKL
Benign
0.013
N
LIST_S2
Benign
0.17
.;T;T
M_CAP
Benign
0.0031
T
MetaRNN
Benign
0.095
T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.14
N;.;N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-2.2
N;D;N
REVEL
Benign
0.042
Sift
Benign
0.18
T;D;T
Sift4G
Benign
0.16
T;D;T
Polyphen
0.73
P;.;P
Vest4
0.23
MVP
0.45
MPC
0.14
ClinPred
0.033
T
GERP RS
3.0
Varity_R
0.034
gMVP
0.038

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.13
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: rs370817737; hg19: chr10-44104781; COSMIC: COSV62424718; COSMIC: COSV62424718; API