19-57634719-G-A

Position:

• chr19-57634719-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001265599.3(ZNF211):​c.-3G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000619 in 1,454,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: ZNF211 NM_001265599.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.879

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38407856).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF211	NM_006385.5	c.220G>A	p.Val74Met	missense_variant	3/4	ENST00000240731.5	NP_006376.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF211	ENST00000240731.5	c.220G>A	p.Val74Met	missense_variant	3/4	2	NM_006385.5	ENSP00000240731.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000619 AC: 9 AN: 1454596 Hom.: 0 Cov.: 30 AF XY: 0.00000553 AC XY: 4 AN XY: 723720

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: 0.00000812

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Aug 19, 2024

The c.220G>A (p.V74M) alteration is located in exon 3 (coding exon 3) of the ZNF211 gene. This alteration results from a G to A substitution at nucleotide position 220, causing the valine (V) at amino acid position 74 to be replaced by a methionine (M). 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	Uncertain	0.52
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	.;T;.;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.38	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.5	.;H;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.6	.;D;D;D
REVEL	Benign	0.25
Sift	Uncertain	0.0010	.;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		1.0	.;D;.;.
Vest4		0.44
MutPred		0.66		Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);.;.;
MVP		0.40
MPC		0.47
ClinPred		0.98	D
GERP RS		2.9
Varity_R		0.26
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr19-58146087;