Genetic Variant ZNF844:p.Leu51Ser (chr19-12075333-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000441304.2(ZNF844):c.152T>C(p.Leu51Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,463,466 control chromosomes in the GnomAD database, including 28,569 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 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: 𝑓 0.28 ( 9355 hom., cov: 33)

Exomes 𝑓: 0.15 ( 19214 hom. )

Consequence

ZNF844
ENST00000441304.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.04

Publications

11 publications found

Variant links:

Genes affected

ZNF844 (HGNC:25932): (zinc finger protein 844) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription 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]

ZNF844 links:

ENSG00000286098 (HGNC:):

ENSG00000286098 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.9675097E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF844	NM_001136501.3 link	c.213T>C	p.Val71Val	synonymous_variant	Exon 4 of 4	ENST00000439326.8	NP_001129973.1
ZNF844	NR_134326.2 link	n.295T>C		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ZNF844	ENST00000439326.8 link	c.213T>C	p.Val71Val	synonymous_variant	Exon 4 of 4	1	NM_001136501.3	ENSP00000392024.3
ENSG00000286098	ENST00000652448.1 link	c.117T>C	p.Val39Val	synonymous_variant	Exon 5 of 5			ENSP00000498410.1
ENSG00000286132	ENST00000651606.1 link	n.6T>C		non_coding_transcript_exon_variant	Exon 1 of 5			ENSP00000498244.1

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

41823

AN:

152042

Hom.:

9313

Cov.:

show subpopulations

Gnomad AFR

AF:

0.620

Gnomad AMI

AF:

0.266

Gnomad AMR

AF:

0.167

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.0764

Gnomad SAS

AF:

0.149

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.249

GnomAD2 exomes

AF:

0.166

AC:

18140

AN:

109232

AF XY:

0.158

show subpopulations

Gnomad AFR exome

AF:

0.629

Gnomad AMR exome

AF:

0.112

Gnomad ASJ exome

AF:

0.173

Gnomad EAS exome

AF:

0.0730

Gnomad FIN exome

AF:

0.125

Gnomad NFE exome

AF:

0.139

Gnomad OTH exome

AF:

0.161

GnomAD4 exome

AF:

0.152

AC:

199041

AN:

1311306

Hom.:

19214

Cov.:

AF XY:

0.150

AC XY:

96365

AN XY:

640412

show subpopulations

African (AFR)

AF:

0.632

AC:

18004

AN:

28468

American (AMR)

AF:

0.127

AC:

2532

AN:

19986

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

3654

AN:

20820

East Asian (EAS)

AF:

0.0937

AC:

3215

AN:

34300

South Asian (SAS)

AF:

0.148

AC:

9543

AN:

64338

European-Finnish (FIN)

AF:

0.126

AC:

5869

AN:

46456

Middle Eastern (MID)

AF:

0.226

AC:

1205

AN:

5324

European-Non Finnish (NFE)

AF:

0.140

AC:

145577

AN:

1037658

Other (OTH)

AF:

0.175

AC:

9442

AN:

53956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

7404

14807

22211

29614

37018

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5638

11276

16914

22552

28190

<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:

0.275

AC:

41910

AN:

152160

Hom.:

9355

Cov.:

AF XY:

0.270

AC XY:

20116

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.620

AC:

25754

AN:

41510

American (AMR)

AF:

0.167

AC:

2547

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

645

AN:

3470

East Asian (EAS)

AF:

0.0764

AC:

396

AN:

5186

South Asian (SAS)

AF:

0.148

AC:

713

AN:

4828

European-Finnish (FIN)

AF:

0.129

AC:

1365

AN:

10572

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.142

AC:

9643

AN:

68006

Other (OTH)

AF:

0.250

AC:

527

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1199

2398

3596

4795

5994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

364

728

1092

1456

1820

<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:

0.194

Hom.:

6822

Bravo

AF:

0.292

TwinsUK

AF:

0.146

AC:

542

ALSPAC

AF:

0.157

AC:

604

ESP6500AA

AF:

0.606

AC:

839

ESP6500EA

AF:

0.131

AC:

416

ExAC

AF:

0.126

AC:

13335

Asia WGS

AF:

0.177

AC:

618

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.44

(source)

DANN

Benign

0.22

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.000010

LIST_S2

Benign

0.067

MetaRNN

Benign

0.000020

MetaSVM

Benign

-1.1

PhyloP100

-1.0

PROVEAN

Benign

3.0

REVEL

Benign

0.020

Sift

Benign

0.43

Sift4G

Benign

0.49

Vest4

0.013

ClinPred

0.00032

GERP RS

-0.94

Mutation Taster

=99/1

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over