19-51993196-T-C

Variant summary

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

The NM_001199324.2(ZNF615):​c.1913A>G​(p.Asn638Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N638I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF615
NM_001199324.2 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.93

Publications

0 publications found
Variant links:
Genes affected
ZNF615 (HGNC:24740): (zinc finger protein 615) 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 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=0.02232793).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF615NM_001199324.2 linkc.1913A>G p.Asn638Ser missense_variant Exon 7 of 7 ENST00000598071.6 NP_001186253.1 Q8N8J6-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF615ENST00000598071.6 linkc.1913A>G p.Asn638Ser missense_variant Exon 7 of 7 1 NM_001199324.2 ENSP00000471041.1 Q8N8J6-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461886
Hom.:
0
Cov.:
37
AF XY:
0.00000138
AC XY:
1
AN XY:
727240
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39698
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1112008
Other (OTH)
AF:
0.00
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.063
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
0.15
DANN
Benign
0.24
DEOGEN2
Benign
0.0039
T;.;T;.;.;.;.
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.00015
N
LIST_S2
Benign
0.093
.;.;T;T;.;T;T
M_CAP
Benign
0.00090
T
MetaRNN
Benign
0.022
T;T;T;T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.27
N;.;N;.;.;.;.
PhyloP100
-2.9
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-0.74
.;.;N;N;.;.;.
REVEL
Benign
0.021
Sift
Benign
0.91
.;.;T;T;.;.;.
Sift4G
Benign
0.50
T;T;T;T;T;T;T
Polyphen
0.011
B;B;B;.;B;.;B
Vest4
0.046
MutPred
0.20
Gain of ubiquitination at K622 (P = 0.078);.;Gain of ubiquitination at K622 (P = 0.078);.;.;.;.;
MVP
0.085
MPC
0.032
ClinPred
0.048
T
GERP RS
-0.17
Varity_R
0.020
gMVP
0.0094
Mutation Taster
=100/0
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: rs2086289403; hg19: chr19-52496449; COSMIC: COSV100943795; COSMIC: COSV100943795; API