19-56577015-G-A

Position:

• chr19-56577015-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001001668.4(ZNF470):​c.586G>A​(p.Glu196Lys) 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. 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: 32)
• Consequence: ZNF470 NM_001001668.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28

Genes affected

ZNF470 (HGNC:22220): (zinc finger protein 470) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08631635).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF470	NM_001001668.4	c.586G>A	p.Glu196Lys	missense_variant	6/6	ENST00000330619.13	NP_001001668.3
ZNF470	XM_047438804.1	c.586G>A	p.Glu196Lys	missense_variant	7/7		XP_047294760.1
ZNF470	XM_047438805.1	c.433G>A	p.Glu145Lys	missense_variant	5/5		XP_047294761.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF470	ENST00000330619.13	c.586G>A	p.Glu196Lys	missense_variant	6/6	1	NM_001001668.4	ENSP00000333223	P1

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

Feb 06, 2024

The c.586G>A (p.E196K) alteration is located in exon 6 (coding exon 4) of the ZNF470 gene. This alteration results from a G to A substitution at nucleotide position 586, causing the glutamic acid (E) at amino acid position 196 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	0.072
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.61
DEOGEN2	Benign	0.0011	T;T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.11	.;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.086	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.81	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.73	N;N
REVEL	Benign	0.039
Sift	Benign	0.54	T;T
Sift4G	Benign	0.80	T;T
Polyphen		0.0	B;B
Vest4		0.13
MutPred		0.56		Gain of MoRF binding (P = 0.0231);Gain of MoRF binding (P = 0.0231);
MVP		0.34
MPC		0.013
ClinPred		0.037	T
GERP RS		1.9
Varity_R		0.068
gMVP		0.072

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: chr19-57088383; COSMIC: COSV57970743;