Variant 19-57641078-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006385.5(ZNF211):c.631A>G(p.Met211Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.000010 ( 0 hom. )

Consequence

ZNF211
NM_006385.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.14

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:

ZNF211 (HGNC:):

ZNF211 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04163888).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF211	NM_006385.5 linkuse as main transcript	c.631A>G	p.Met211Val	missense_variant	4/4	ENST00000240731.5	NP_006376.2	Q13398-7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF211	ENST00000240731.5 linkuse as main transcript	c.631A>G	p.Met211Val	missense_variant	4/4	2	NM_006385.5	ENSP00000240731.4		Q13398-7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

251042

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135688

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:

0.0000103

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

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 submitter

clinical testing

Ambry Genetics

Jan 22, 2024

The c.631A>G (p.M211V) alteration is located in exon 4 (coding exon 4) of the ZNF211 gene. This alteration results from a A to G substitution at nucleotide position 631, causing the methionine (M) at amino acid position 211 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

0.072

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.0030

DANN

Benign

0.34

DEOGEN2

Benign

0.0055

.;T;.;.;.;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.011

T;T;T;T;T;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.042

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.58

.;N;.;.;.;.

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.7

.;N;N;N;N;N

REVEL

Benign

0.015

Sift

Benign

0.82

.;T;T;T;T;T

Sift4G

Benign

0.51

T;T;T;T;T;T

Polyphen

0.0, 0.47

.;B;P;.;.;.

Vest4

0.13

MutPred

0.56

.;Loss of stability (P = 0.1848);.;.;.;.;

MVP

0.076

MPC

0.086

ClinPred

0.017

GERP RS

-6.5

Varity_R

0.030

gMVP

0.10

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