chr19-53576890-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001079906.2(ZNF331):​c.330A>T​(p.Arg110Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ZNF331
NM_001079906.2 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.643

Publications

24 publications found
Variant links:
Genes affected
ZNF331 (HGNC:15489): (zinc finger protein 331) This gene encodes a zinc finger protein containing a KRAB (Kruppel-associated box) domain found in transcriptional repressors. This gene may be methylated and silenced in cancer cells. This gene is located within a differentially methylated region (DMR) and shows allele-specific expression in placenta. Alternative splicing and the use of alternative promoters results in multiple transcript variants encoding the same protein. [provided by RefSeq, Nov 2015]

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.054951817).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF331NM_001079906.2 linkc.330A>T p.Arg110Ser missense_variant Exon 6 of 6 ENST00000449416.6 NP_001073375.1 Q9NQX6A0A024R4J5Q71QC5Q68D63

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF331ENST00000449416.6 linkc.330A>T p.Arg110Ser missense_variant Exon 6 of 6 5 NM_001079906.2 ENSP00000393817.1 Q9NQX6

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461868
Hom.:
0
Cov.:
58
AF XY:
0.00000275
AC XY:
2
AN XY:
727238
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44714
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00000360
AC:
4
AN:
1112000
Other (OTH)
AF:
0.00
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.485
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
0.17
DANN
Benign
0.86
DEOGEN2
Benign
0.056
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.026
N
LIST_S2
Benign
0.11
.;.;.;.;T;.;.;.;.;.;.;T;.;.;.
M_CAP
Benign
0.0011
T
MetaRNN
Benign
0.055
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.3
L;L;L;L;L;L;L;L;L;L;.;.;L;L;L
PhyloP100
-0.64
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-0.15
.;N;.;N;N;N;N;.;N;N;N;N;.;.;.
REVEL
Benign
0.034
Sift
Benign
0.64
.;T;.;T;T;T;T;.;T;T;T;T;.;.;.
Sift4G
Benign
0.31
.;T;.;T;T;T;T;.;T;T;T;T;.;.;.
Polyphen
0.0
B;B;B;B;B;B;B;B;B;B;.;.;B;B;B
Vest4
0.072, 0.088, 0.078, 0.087, 0.075, 0.073
MutPred
0.47
Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);
MVP
0.38
MPC
0.68
ClinPred
0.033
T
GERP RS
-5.3
Varity_R
0.057
gMVP
0.12
Mutation Taster
=99/1
polymorphism

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

Other links and lift over

dbSNP: rs8109631; hg19: chr19-54080144; API