chr16-71861807-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001201552.2(ZNF821):c.553G>A(p.Ala185Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000145 in 1,614,128 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 4 hom. )

Consequence

ZNF821
NM_001201552.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.06

Publications

0 publications found

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]

ZNF821 links:

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]

IST1 links:

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]

ATXN1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016641885).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001201552.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF821	NM_001201552.2	MANE Select	c.553G>A	p.Ala185Thr	missense	Exon 7 of 8	NP_001188481.1	O75541-1
ZNF821	NM_001201553.1		c.553G>A	p.Ala185Thr	missense	Exon 6 of 7	NP_001188482.1	O75541-1
ZNF821	NM_001376297.1		c.553G>A	p.Ala185Thr	missense	Exon 7 of 8	NP_001363226.1	O75541-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF821	ENST00000425432.6	TSL:5 MANE Select	c.553G>A	p.Ala185Thr	missense	Exon 7 of 8	ENSP00000398089.1	O75541-1
ZNF821	ENST00000313565.10	TSL:1	c.427G>A	p.Ala143Thr	missense	Exon 6 of 7	ENSP00000313822.6	A0A0C4DH12
ZNF821	ENST00000446827.6	TSL:1	c.427G>A	p.Ala143Thr	missense	Exon 5 of 6	ENSP00000405908.2	A0A0C4DH12

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000231

AC:

AN:

251444

AF XY:

0.000338

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000151

AC:

221

AN:

1461848

Hom.:

Cov.:

AF XY:

0.000224

AC XY:

163

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00245

AC:

211

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112012

Other (OTH)

AF:

0.000166

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0000854

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41550

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00269

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000522

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.000305

AC:

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.030

Eigen

Benign

-0.0087

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.013

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PhyloP100

3.1

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.67

REVEL

Benign

0.054

Sift

Benign

0.063

Sift4G

Pathogenic

0.0

Polyphen

0.0030

Vest4

0.26

MutPred

0.47

Gain of helix (P = 0.132)

MVP

0.040

MPC

0.85

ClinPred

0.057

GERP RS

4.2

Varity_R

0.094

gMVP

0.47

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over