11-3359827-C-G

Variant summary

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

The NM_001130520.3(ZNF195):​c.1181G>C​(p.Ser394Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000985 in 1,614,002 control chromosomes in the GnomAD database, including 1 homozygotes. 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 (★).

Frequency

Genomes: 𝑓 0.00042 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

ZNF195
NM_001130520.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.836
Variant links:
Genes affected
ZNF195 (HGNC:12986): (zinc finger protein 195) This gene encodes a protein belonging to the Krueppel C2H2-type zinc-finger protein family. These family members are transcription factors that are implicated in a variety of cellular processes. This gene is located near the centromeric border of chromosome 11p15.5, next to an imprinted domain that is associated with maternal-specific loss of heterozygosity in Wilms' tumors. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

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=0.0069962144).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF195NM_001130520.3 linkc.1181G>C p.Ser394Thr missense_variant Exon 6 of 6 ENST00000399602.9 NP_001123992.1 O14628-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF195ENST00000399602.9 linkc.1181G>C p.Ser394Thr missense_variant Exon 6 of 6 1 NM_001130520.3 ENSP00000382511.4 O14628-1

Frequencies

GnomAD3 genomes
AF:
0.000362
AC:
55
AN:
152118
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00126
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
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:
0.00
GnomAD3 exomes
AF:
0.000156
AC:
39
AN:
249264
Hom.:
0
AF XY:
0.000118
AC XY:
16
AN XY:
135238
show subpopulations
Gnomad AFR exome
AF:
0.00188
Gnomad AMR exome
AF:
0.000232
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000650
AC:
95
AN:
1461762
Hom.:
0
Cov.:
31
AF XY:
0.0000481
AC XY:
35
AN XY:
727172
show subpopulations
Gnomad4 AFR exome
AF:
0.00182
Gnomad4 AMR exome
AF:
0.000179
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.000364
GnomAD4 genome
AF:
0.000420
AC:
64
AN:
152240
Hom.:
1
Cov.:
32
AF XY:
0.000470
AC XY:
35
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.00147
Gnomad4 AMR
AF:
0.000196
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:
0.00
Alfa
AF:
0.0000339
Hom.:
0
Bravo
AF:
0.000468
ESP6500AA
AF:
0.00127
AC:
5
ESP6500EA
AF:
0.000120
AC:
1
ExAC
AF:
0.000165
AC:
20
Asia WGS
AF:
0.00289
AC:
10
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 17, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1181G>C (p.S394T) alteration is located in exon 6 (coding exon 6) of the ZNF195 gene. This alteration results from a G to C substitution at nucleotide position 1181, causing the serine (S) at amino acid position 394 to be replaced by a threonine (T). 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
0.20
BayesDel_addAF
Benign
-0.66
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
1.1
DANN
Benign
0.68
DEOGEN2
Benign
0.027
.;.;T;T;.;.;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.000040
N
LIST_S2
Benign
0.022
T;T;T;T;.;T;T
M_CAP
Benign
0.00080
T
MetaRNN
Benign
0.0070
T;T;T;T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.9
.;.;.;L;.;.;.
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-1.7
N;N;.;N;N;N;N
REVEL
Benign
0.013
Sift
Benign
0.052
T;T;.;D;T;T;T
Sift4G
Benign
0.12
T;T;T;T;T;T;T
Polyphen
0.0010
B;B;.;B;B;B;B
Vest4
0.063
MVP
0.25
MPC
0.20
ClinPred
0.0023
T
GERP RS
-0.033
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.072
gMVP
0.027

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: rs116076465; hg19: chr11-3381057; API