chr19-57537515-A-C

Position:

• chr19-57537515-A-C

Variant summary

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

The NM_001199295.2(ZNF549):​c.511A>C​(p.Asn171His) 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: ZNF549 NM_001199295.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.979

Genes affected

ZNF549 (HGNC:26632): (zinc finger protein 549) 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]

ZNF550 (HGNC:28643): (zinc finger protein 550) 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]

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=0.08100441).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF549	NM_001199295.2	c.511A>C	p.Asn171His	missense_variant	4/4	ENST00000376233.8	NP_001186224.2
ZNF549	NM_153263.3	c.472A>C	p.Asn158His	missense_variant	3/3		NP_694995.3
ZNF549	XM_047438563.1	c.598A>C	p.Asn200His	missense_variant	3/3		XP_047294519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF549	ENST00000376233.8	c.511A>C	p.Asn171His	missense_variant	4/4	1	NM_001199295.2	ENSP00000365407.2

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

Jun 29, 2023

The c.511A>C (p.N171H) alteration is located in exon 4 (coding exon 4) of the ZNF549 gene. This alteration results from a A to C substitution at nucleotide position 511, causing the asparagine (N) at amino acid position 171 to be replaced by a histidine (H). 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	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.5
DANN	Benign	0.93
DEOGEN2	Benign	0.015	.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.081	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.21	.;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.016
Sift	Uncertain	0.013	D;D
Sift4G	Uncertain	0.013	D;D
Polyphen		0.0	B;B
Vest4		0.11
MutPred		0.26		.;Gain of ubiquitination at K174 (P = 0.135);
MVP		0.13
MPC		0.068
ClinPred		0.089	T
GERP RS		2.1
Varity_R		0.082
gMVP		0.048

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: chr19-58048883;