19-30548762-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014717.3(ZNF536):​c.3143C>T​(p.Ala1048Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0358 in 1,613,832 control chromosomes in the GnomAD database, including 1,508 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 Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 135 hom., cov: 33)
Exomes 𝑓: 0.036 ( 1373 hom. )

Consequence

ZNF536
NM_014717.3 missense

Scores

18

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0720

Publications

14 publications found
Variant links:
Genes affected
ZNF536 (HGNC:29025): (zinc finger protein 536) The protein encoded by this gene is a highly conserved zinc finger protein. The encoded protein is most abundant in brain, where it negatively regulates neuronal differentiation. [provided by RefSeq, Sep 2015]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0017009676).
BP6
Variant 19-30548762-C-T is Benign according to our data. Variant chr19-30548762-C-T is described in ClinVar as [Benign]. Clinvar id is 403626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF536NM_014717.3 linkc.3143C>T p.Ala1048Val missense_variant Exon 4 of 5 ENST00000355537.4 NP_055532.1 O15090

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF536ENST00000355537.4 linkc.3143C>T p.Ala1048Val missense_variant Exon 4 of 5 1 NM_014717.3 ENSP00000347730.1 O15090

Frequencies

GnomAD3 genomes
AF:
0.0330
AC:
5024
AN:
152096
Hom.:
135
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0314
Gnomad AMI
AF:
0.0373
Gnomad AMR
AF:
0.0228
Gnomad ASJ
AF:
0.0187
Gnomad EAS
AF:
0.00368
Gnomad SAS
AF:
0.121
Gnomad FIN
AF:
0.0200
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0352
Gnomad OTH
AF:
0.0306
GnomAD2 exomes
AF:
0.0364
AC:
9128
AN:
251030
AF XY:
0.0401
show subpopulations
Gnomad AFR exome
AF:
0.0340
Gnomad AMR exome
AF:
0.0172
Gnomad ASJ exome
AF:
0.0185
Gnomad EAS exome
AF:
0.00315
Gnomad FIN exome
AF:
0.0200
Gnomad NFE exome
AF:
0.0321
Gnomad OTH exome
AF:
0.0344
GnomAD4 exome
AF:
0.0361
AC:
52831
AN:
1461618
Hom.:
1373
Cov.:
33
AF XY:
0.0382
AC XY:
27804
AN XY:
727084
show subpopulations
African (AFR)
AF:
0.0319
AC:
1067
AN:
33480
American (AMR)
AF:
0.0179
AC:
802
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.0188
AC:
492
AN:
26136
East Asian (EAS)
AF:
0.00186
AC:
74
AN:
39700
South Asian (SAS)
AF:
0.110
AC:
9507
AN:
86258
European-Finnish (FIN)
AF:
0.0202
AC:
1072
AN:
53152
Middle Eastern (MID)
AF:
0.0147
AC:
85
AN:
5768
European-Non Finnish (NFE)
AF:
0.0339
AC:
37678
AN:
1112004
Other (OTH)
AF:
0.0340
AC:
2054
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.472
Heterozygous variant carriers
0
3366
6733
10099
13466
16832
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
1444
2888
4332
5776
7220
<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
AF:
0.0330
AC:
5024
AN:
152214
Hom.:
135
Cov.:
33
AF XY:
0.0338
AC XY:
2512
AN XY:
74422
show subpopulations
African (AFR)
AF:
0.0314
AC:
1303
AN:
41552
American (AMR)
AF:
0.0227
AC:
347
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.0187
AC:
65
AN:
3472
East Asian (EAS)
AF:
0.00349
AC:
18
AN:
5152
South Asian (SAS)
AF:
0.121
AC:
585
AN:
4822
European-Finnish (FIN)
AF:
0.0200
AC:
212
AN:
10616
Middle Eastern (MID)
AF:
0.00340
AC:
1
AN:
294
European-Non Finnish (NFE)
AF:
0.0352
AC:
2395
AN:
67992
Other (OTH)
AF:
0.0303
AC:
64
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
248
496
745
993
1241
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
70
140
210
280
350
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0313
Hom.:
274
Bravo
AF:
0.0297
TwinsUK
AF:
0.0324
AC:
120
ALSPAC
AF:
0.0324
AC:
125
ESP6500AA
AF:
0.0365
AC:
161
ESP6500EA
AF:
0.0335
AC:
288
ExAC
AF:
0.0383
AC:
4653
Asia WGS
AF:
0.0600
AC:
208
AN:
3478
EpiCase
AF:
0.0322
EpiControl
AF:
0.0317

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Mar 29, 2016
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.075
BayesDel_addAF
Benign
-0.81
T
BayesDel_noAF
Benign
-0.85
CADD
Benign
8.7
DANN
Benign
0.89
DEOGEN2
Benign
0.032
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.60
T
MetaRNN
Benign
0.0017
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.20
N
PhyloP100
0.072
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.89
N
REVEL
Benign
0.025
Sift
Benign
0.12
T
Sift4G
Benign
0.11
T
Polyphen
0.0020
B
Vest4
0.022
MPC
0.12
ClinPred
0.0026
T
GERP RS
0.61
Varity_R
0.025
gMVP
0.27
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs77238711; hg19: chr19-31039669; COSMIC: COSV62835849; COSMIC: COSV62835849; API