19-12135823-T-G

Position:

• chr19-12135823-T-G

Variant summary

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

The ENST00000334213.10(ZNF20):​c.85A>C​(p.Lys29Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF20 ENST00000334213.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.878

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34757882).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF20	NM_021143.4	c.85A>C	p.Lys29Gln	missense_variant	2/4	ENST00000334213.10	NP_066966.2
ZNF625-ZNF20	NR_037802.1	n.667A>C		non_coding_transcript_exon_variant	6/8
ZNF20	NM_001203250.2	c.76A>C	p.Lys26Gln	missense_variant	2/4		NP_001190179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF20	ENST00000334213.10	c.85A>C	p.Lys29Gln	missense_variant	2/4	1	NM_021143.4	ENSP00000335437	P1
	ENST00000601686.1	n.213T>G		non_coding_transcript_exon_variant	2/3	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Nov 09, 2021

The c.85A>C (p.K29Q) alteration is located in exon 2 (coding exon 2) of the ZNF20 gene. This alteration results from a A to C substitution at nucleotide position 85, causing the lysine (K) at amino acid position 29 to be replaced by a glutamine (Q). 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	0.22
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.074	.;T;T
Eigen	Benign	0.0048
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.082	T;T;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	.;M;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.3	.;D;D
REVEL	Benign	0.068
Sift	Uncertain	0.0020	.;D;D
Sift4G	Uncertain	0.032	D;D;.
Polyphen		0.99	.;D;.
Vest4		0.27
MutPred		0.64		.;Loss of methylation at K29 (P = 0.0053);.;
MVP		0.40
MPC		0.74
ClinPred		0.73	D
GERP RS		0.94
Varity_R		0.36
gMVP		0.15

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: chr19-12246638;