chr19-57686837-C-G

Position:

• chr19-57686837-C-G

Variant summary

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

The NM_138347.5(ZNF551):​c.562C>G​(p.Pro188Ala) 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 NM_138347.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.54

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 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=0.08078626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF551	NM_138347.5	c.562C>G	p.Pro188Ala	missense_variant	3/3	ENST00000282296.10	NP_612356.2
ZNF551	NM_001270938.2	c.478C>G	p.Pro160Ala	missense_variant	3/3		NP_001257867.1
ZNF551	NR_073102.2	n.625C>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.562C>G	p.Pro188Ala	missense_variant	3/3	1	NM_138347.5	ENSP00000282296	P1
ZNF551	ENST00000601064.1	c.478C>G	p.Pro160Ala	missense_variant	3/3	1		ENSP00000472674
ZNF551	ENST00000596085.1	c.157+1452C>G		intron_variant		2		ENSP00000472230
ZNF551	ENST00000599402.1			downstream_gene_variant		1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Sep 13, 2023

The c.514C>G (p.P172A) alteration is located in exon 3 (coding exon 3) of the ZNF551 gene. This alteration results from a C to G substitution at nucleotide position 514, causing the proline (P) at amino acid position 172 to be replaced by an alanine (A). 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	0.058
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.027
DANN	Benign	0.73
DEOGEN2	Benign	0.0028	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.063	T;T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.081	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.93	.;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.19	T
REVEL	Benign	0.0050
Sift4G	Benign	0.74	T;T
Polyphen		0.21	.;B
Vest4		0.14
MutPred		0.25		.;Loss of glycosylation at T191 (P = 0.0772);
MVP		0.11
MPC		0.11
ClinPred		0.12	T
GERP RS		-0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.046
gMVP		0.0044

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: chr19-58198205;