19-12135874-C-T

Position:

• chr19-12135874-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000334213.10(ZNF20):​c.34G>A​(p.Val12Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF20 ENST00000334213.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.59

Genes affected

ZNF20 (HGNC:12992): (zinc finger protein 20) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF20	NM_021143.4	c.34G>A	p.Val12Met	missense_variant	2/4	ENST00000334213.10	NP_066966.2
ZNF625-ZNF20	NR_037802.1	n.616G>A		non_coding_transcript_exon_variant	6/8
ZNF20	NM_001203250.2	c.25G>A	p.Val9Met	missense_variant	2/4		NP_001190179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF20	ENST00000334213.10	c.34G>A	p.Val12Met	missense_variant	2/4	1	NM_021143.4	ENSP00000335437	P1
	ENST00000601686.1	n.264C>T		non_coding_transcript_exon_variant	2/3	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1461852 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727230

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: 0.00

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

Dec 11, 2023

The c.34G>A (p.V12M) alteration is located in exon 2 (coding exon 2) of the ZNF20 gene. This alteration results from a G to A substitution at nucleotide position 34, causing the valine (V) at amino acid position 12 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	Pathogenic	0.67
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	.;T;T
Eigen	Uncertain	0.24
Eigen_PC	Benign	-0.039
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.82	T;T;D
M_CAP	Benign	0.0029	T
MetaRNN	Uncertain	0.66	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	.;M;.
MutationTaster	Benign	0.94	N
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.6	.;D;D
REVEL	Benign	0.14
Sift	Pathogenic	0.0	.;D;D
Sift4G	Pathogenic	0.0010	D;D;.
Polyphen		1.0	.;D;.
Vest4		0.38
MutPred		0.78		.;Gain of disorder (P = 0.0781);.;
MVP		0.38
MPC		0.71
ClinPred		0.93	D
GERP RS		0.94
Varity_R		0.29
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr19-12246689;