16-71867995-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001201552.2(ZNF821):​c.83C>T​(p.Ala28Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000737 in 1,383,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

ZNF821
NM_001201552.2 missense

Scores

10
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.69
Variant links:
Genes affected
ZNF821 (HGNC:28043): (zinc finger protein 821) This gene encodes a protein with two C2H2 zinc finger motifs and a score-and-three (23)-amino acid peptide repeat (STPR) domain. The STPR domain of the encoded protein binds to double stranded DNA and may also contain a nuclear localization signal, suggesting that this protein interacts with chromosomal DNA. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]
IST1 (HGNC:28977): (IST1 factor associated with ESCRT-III) This gene encodes a protein with MIT-interacting motifs that interacts with components of endosomal sorting complexes required for transport (ESCRT). ESCRT functions in vesicle budding, such as that which occurs during membrane abscission in cytokinesis. There is a pseudogene for this gene on chromosome 19. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]
ATXN1L (HGNC:33279): (ataxin 1 like) Predicted to enable DNA binding activity and RNA binding activity. Predicted to be involved in several processes, including learning or memory; regulation of transcription, DNA-templated; and social behavior. Predicted to act upstream of or within several processes, including lung alveolus development; negative regulation of transcription by RNA polymerase II; and positive regulation of hematopoietic stem cell proliferation. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.25409687).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF821NM_001201552.2 linkuse as main transcriptc.83C>T p.Ala28Val missense_variant 4/8 ENST00000425432.6 NP_001188481.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF821ENST00000425432.6 linkuse as main transcriptc.83C>T p.Ala28Val missense_variant 4/85 NM_001201552.2 ENSP00000398089 P4O75541-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000745
AC:
1
AN:
134270
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
73142
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000189
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000737
AC:
102
AN:
1383566
Hom.:
0
Cov.:
30
AF XY:
0.0000850
AC XY:
58
AN XY:
682720
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000126
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000918
Gnomad4 OTH exome
AF:
0.0000345
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000302

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 06, 2023The c.83C>T (p.A28V) alteration is located in exon 4 (coding exon 2) of the ZNF821 gene. This alteration results from a C to T substitution at nucleotide position 83, causing the alanine (A) at amino acid position 28 to be replaced by a valine (V). 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
0.31
BayesDel_addAF
Uncertain
0.029
T
BayesDel_noAF
Benign
-0.17
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.035
.;T;.;T;.;.;.
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.91
D;D;D;.;D;.;D
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.25
T;T;T;T;T;T;T
MetaSVM
Uncertain
0.10
D
MutationAssessor
Benign
0.55
.;N;.;N;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-0.26
.;N;D;N;N;D;D
REVEL
Uncertain
0.33
Sift
Uncertain
0.0050
.;D;D;D;D;D;D
Sift4G
Benign
0.41
T;T;T;T;.;.;.
Vest4
0.64
MutPred
0.24
Loss of disorder (P = 0.1374);Loss of disorder (P = 0.1374);Loss of disorder (P = 0.1374);Loss of disorder (P = 0.1374);Loss of disorder (P = 0.1374);Loss of disorder (P = 0.1374);Loss of disorder (P = 0.1374);
MVP
0.23
MPC
1.9
ClinPred
0.62
D
GERP RS
6.0
Varity_R
0.11
gMVP
0.35

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs1367448441; hg19: chr16-71901898; API