Genetic Variant ZNF836:p.Phe899Ser (chr19-52154987-A-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001102657.3(ZNF836):c.2696T>C(p.Phe899Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. F899Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZNF836
NM_001102657.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.190

Publications

0 publications found

Variant links:

Genes affected

ZNF836 (HGNC:34333): (zinc finger protein 836) 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]

ZNF836 links:

ENSG00000267827 (HGNC:):

ENSG00000267827 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.78

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF836	NM_001102657.3 link	c.2696T>C	p.Phe899Ser	missense_variant	Exon 5 of 5	ENST00000682614.1	NP_001096127.1	Q6ZNA1
ZNF836	XM_011526558.4 link	c.2696T>C	p.Phe899Ser	missense_variant	Exon 5 of 5		XP_011524860.1	Q6ZNA1
ZNF836	XM_011526559.4 link	c.2696T>C	p.Phe899Ser	missense_variant	Exon 4 of 4		XP_011524861.1	Q6ZNA1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF836	ENST00000682614.1 link	c.2696T>C	p.Phe899Ser	missense_variant	Exon 5 of 5		NM_001102657.3	ENSP00000507838.1		Q6ZNA1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

248688

AF XY:

0.00000741

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:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459368

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725752

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33376

American (AMR)

AF:

0.00

AC:

AN:

44390

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26000

East Asian (EAS)

AF:

0.00

AC:

AN:

39658

South Asian (SAS)

AF:

0.00

AC:

AN:

85926

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110590

Other (OTH)

AF:

0.00

AC:

AN:

60284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

T;.

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.0050

LIST_S2

Benign

0.63

T;T

M_CAP

Benign

0.0014

MetaRNN

Pathogenic

0.78

D;D

MetaSVM

Benign

-0.91

MutationAssessor

Pathogenic

3.1

M;.

PhyloP100

0.19

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-4.7

.;D

REVEL

Benign

0.13

Sift

Uncertain

0.0010

.;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.68

P;.

Vest4

0.33

MutPred

0.84

Gain of disorder (P = 0.0148);Gain of disorder (P = 0.0148);

MVP

0.28

MPC

0.32

ClinPred

0.73

GERP RS

-2.0

Varity_R

0.57

gMVP

0.089

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over