chr19-57687170-A-G

Position:

• chr19-57687170-A-G

Variant summary

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

The ENST00000282296.10(ZNF551):​c.895A>G​(p.Ile299Val) 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. 14/20 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)
• Consequence: ZNF551 ENST00000282296.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.322

Genes affected

ZNF551 (HGNC:25108): (zinc finger protein 551) 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. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.067211).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF551	NM_138347.5	c.895A>G	p.Ile299Val	missense_variant	3/3	ENST00000282296.10	NP_612356.2
ZNF551	NM_001270938.2	c.811A>G	p.Ile271Val	missense_variant	3/3		NP_001257867.1
ZNF551	NR_073102.2	n.958A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF551	ENST00000282296.10	c.895A>G	p.Ile299Val	missense_variant	3/3	1	NM_138347.5	ENSP00000282296	P1
ZNF551	ENST00000601064.1	c.811A>G	p.Ile271Val	missense_variant	3/3	1		ENSP00000472674
ZNF551	ENST00000596085.1	c.157+1785A>G		intron_variant		2		ENSP00000472230

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

Mar 01, 2023

The c.847A>G (p.I283V) alteration is located in exon 3 (coding exon 3) of the ZNF551 gene. This alteration results from a A to G substitution at nucleotide position 847, causing the isoleucine (I) at amino acid position 283 to be replaced by a valine (V). 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	0.12
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.7
DANN	Benign	0.54
DEOGEN2	Benign	0.010	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0012	N
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.067	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.47	.;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.24	T
REVEL	Benign	0.037
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.062	.;B
Vest4		0.027
MutPred		0.48		.;Gain of ubiquitination at K298 (P = 0.1084);
MVP		0.51
MPC		0.066
ClinPred		0.12	T
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.027
gMVP		0.0080

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: chr19-58198538;