Genetic Variant NM_006385.5:c.289C>T (chr19-57640736-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_006385.5(ZNF211):c.289C>T(p.Pro97Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

ZNF211
NM_006385.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.22

Variant links:

Genes affected

ZNF211 (HGNC:13003): (zinc finger protein 211) This gene encodes a protein containing a Kruppel-associated box domain and multiple zinc finger domains. This protein may play a role in developmental processes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ZNF211 links:

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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=0.11600995).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF211	NM_006385.5 link	c.289C>T	p.Pro97Ser	missense_variant	Exon 4 of 4	ENST00000240731.5	NP_006376.2	Q13398-7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF211	ENST00000240731.5 link	c.289C>T	p.Pro97Ser	missense_variant	Exon 4 of 4	2	NM_006385.5	ENSP00000240731.4		Q13398-7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251324

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135828

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:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000752

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727234

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:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.289C>T (p.P97S) alteration is located in exon 4 (coding exon 4) of the ZNF211 gene. This alteration results from a C to T substitution at nucleotide position 289, causing the proline (P) at amino acid position 97 to be replaced by a serine (S). 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

0.081

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.50

DANN

Benign

0.90

DEOGEN2

Benign

0.064

.;T;.;.;.;.

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.52

T;T;T;T;T;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.12

T;T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.84

.;L;.;.;.;.

PrimateAI

Benign

0.19

PROVEAN

Pathogenic

-5.2

.;D;D;D;D;D

REVEL

Benign

0.028

Sift

Benign

0.12

.;T;T;T;T;T

Sift4G

Benign

0.091

T;T;T;T;T;T

Polyphen

0.81, 0.71

.;P;P;.;.;.

Vest4

0.055

MutPred

0.26

.;Gain of phosphorylation at P84 (P = 0.0563);.;.;.;.;

MVP

0.20

MPC

0.10

ClinPred

0.22

GERP RS

1.2

Varity_R

0.047

gMVP

0.064

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over