10-43608618-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_145312.4(ZNF485):​c.29C>T​(p.Pro10Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,612,978 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

ZNF485
NM_145312.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.600
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 Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.01270777).
BP6
Variant 10-43608618-C-T is Benign according to our data. Variant chr10-43608618-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3196096.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF485NM_145312.4 linkc.29C>T p.Pro10Leu missense_variant Exon 3 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.29C>T p.Pro10Leu missense_variant Exon 3 of 5 1 NM_145312.4 ENSP00000354694.3 Q8NCK3-1
ZNF485ENST00000374435.3 linkc.29C>T p.Pro10Leu missense_variant Exon 3 of 5 1 ENSP00000363558.3 Q8NCK3-1
ZNF485ENST00000430885.5 linkc.29C>T p.Pro10Leu missense_variant Exon 3 of 5 2 ENSP00000393570.1 C9JV60

Frequencies

GnomAD3 genomes
AF:
0.0000855
AC:
13
AN:
152128
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.000565
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000185
AC:
46
AN:
249142
Hom.:
0
AF XY:
0.000149
AC XY:
20
AN XY:
134592
show subpopulations
Gnomad AFR exome
AF:
0.0000621
Gnomad AMR exome
AF:
0.0000292
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000549
Gnomad SAS exome
AF:
0.0000329
Gnomad FIN exome
AF:
0.00139
Gnomad NFE exome
AF:
0.0000800
Gnomad OTH exome
AF:
0.000492
GnomAD4 exome
AF:
0.000140
AC:
204
AN:
1460850
Hom.:
0
Cov.:
30
AF XY:
0.000128
AC XY:
93
AN XY:
726586
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.0000225
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00103
Gnomad4 NFE exome
AF:
0.000122
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000855
AC:
13
AN:
152128
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000565
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000848
Hom.:
0
Bravo
AF:
0.0000604
ExAC
AF:
0.0000988
AC:
12

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Aug 09, 2021
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
0.97
DANN
Benign
0.89
DEOGEN2
Benign
0.0055
T;T;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.0048
N
LIST_S2
Benign
0.14
.;T;T
M_CAP
Benign
0.0033
T
MetaRNN
Benign
0.013
T;T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
-1.0
N;.;N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-1.8
N;N;N
REVEL
Benign
0.053
Sift
Benign
0.41
T;T;T
Sift4G
Benign
0.81
T;T;T
Polyphen
0.47
P;.;P
Vest4
0.074
MVP
0.21
MPC
0.12
ClinPred
0.0091
T
GERP RS
-0.35
Varity_R
0.037
gMVP
0.044

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs780534178; hg19: chr10-44104066; API