chr19-57640779-G-A

Position:

• chr19-57640779-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006385.5(ZNF211):​c.332G>A​(p.Arg111Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,890 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: 0.0000027 (0 hom.)
• Consequence: ZNF211 NM_006385.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.109

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 (HGNC:):

ACMG classification

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=0.06025836).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF211	NM_006385.5	c.332G>A	p.Arg111Lys	missense_variant	4/4	ENST00000240731.5	NP_006376.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF211	ENST00000240731.5	c.332G>A	p.Arg111Lys	missense_variant	4/4	2	NM_006385.5	ENSP00000240731.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461890 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727246

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2021

The c.332G>A (p.R111K) alteration is located in exon 4 (coding exon 4) of the ZNF211 gene. This alteration results from a G to A substitution at nucleotide position 332, causing the arginine (R) at amino acid position 111 to be replaced by a lysine (K). 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	0.10
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	8.4
DANN	Benign	0.91
DEOGEN2	Benign	0.010	.;T;.;.;.;.
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.11	T;T;T;T;T;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.060	T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.92	.;L;.;.;.;.
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.8	.;N;N;N;N;N
REVEL	Benign	0.041
Sift	Benign	0.15	.;T;T;T;T;T
Sift4G	Benign	0.17	T;T;T;T;T;T
Polyphen		0.022, 0.38	.;B;B;.;.;.
Vest4		0.034
MutPred		0.26		.;Gain of methylation at R98 (P = 0.0161);.;.;.;.;
MVP		0.21
MPC		0.086
ClinPred		0.056	T
GERP RS		-3.1
Varity_R		0.056
gMVP		0.042

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-58152147;