19-57686898-G-A

Variant names:

• chr19-57686898-G-A
• rs1600019758
• NM_138347.5:c.623G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138347.5(ZNF551):​c.623G>A​(p.Ser208Asn) 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: 33)
• Consequence: ZNF551 NM_138347.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.334
• Publications: 0 publications found

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]

ENSG00000269026 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.076262).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF551	NM_138347.5	c.623G>A	p.Ser208Asn	missense_variant	Exon 3 of 3	ENST00000282296.10	NP_612356.2
ZNF551	NM_001270938.2	c.539G>A	p.Ser180Asn	missense_variant	Exon 3 of 3		NP_001257867.1
ZNF551	NR_073102.2	n.686G>A		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF551	ENST00000282296.10	c.623G>A	p.Ser208Asn	missense_variant	Exon 3 of 3	1	NM_138347.5	ENSP00000282296.5
ENSG00000269026	ENST00000594684.1	c.33+4654G>A		intron_variant	Intron 1 of 2	1		ENSP00000472160.1

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

Jun 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.575G>A (p.S192N) alteration is located in exon 3 (coding exon 3) of the ZNF551 gene. This alteration results from a G to A substitution at nucleotide position 575, causing the serine (S) at amino acid position 192 to be replaced by an asparagine (N). 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	0.098
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.57
DEOGEN2	Benign	0.010	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.00013	N
LIST_S2	Benign	0.082	T;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.076	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	.;L
PhyloP100		-0.33
PrimateAI	Benign	0.22	T
REVEL	Benign	0.018
Sift4G	Benign	0.57	T;T
Polyphen		0.010	.;B
Vest4		0.065
MutPred		0.33		.;Loss of phosphorylation at S208 (P = 0.0382);
MVP		0.20
MPC		0.14
ClinPred		0.019	T
GERP RS		0.27
Varity_R		0.068
gMVP		0.0046
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1600019758; hg19: chr19-58198266;