chr19-37564658-C-G

Position:

• chr19-37564658-C-G

Variant summary

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

The NM_016536.5(ZNF571):​c.1770G>C​(p.Gln590His) 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: ZNF571 NM_016536.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.22

Genes affected

ZNF571 (HGNC:25000): (zinc finger protein 571) 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 nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF571-AS1 (HGNC:44324): (ZNF571 antisense RNA 1)

ZNF540 (HGNC:25331): (zinc finger protein 540) Enables translation repressor activity, mRNA regulatory element binding. Involved in negative regulation of transcription, DNA-templated and negative regulation of translation. Located in cytosol and nucleoplasm. [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=0.082242936).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF571	NM_016536.5	c.1770G>C	p.Gln590His	missense_variant	4/4	ENST00000451802.7
ZNF571-AS1	NR_038248.1	n.338-1373C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF571	ENST00000451802.7	c.1770G>C	p.Gln590His	missense_variant	4/4	1	NM_016536.5	P1
ZNF571-AS1	ENST00000585578.5	n.210-1373C>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Sep 06, 2022

The c.1770G>C (p.Q590H) alteration is located in exon 4 (coding exon 3) of the ZNF571 gene. This alteration results from a G to C substitution at nucleotide position 1770, causing the glutamine (Q) at amino acid position 590 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	0.14
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.2
DANN	Benign	0.89
DEOGEN2	Benign	0.012	T;T;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.000010	N
LIST_S2	Benign	0.54	T;.;.;.
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.082	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.36	N;N;N;N
MutationTaster	Benign	0.99	D;D;N;N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.7	N;.;N;N
REVEL	Benign	0.024
Sift	Uncertain	0.011	D;.;D;D
Sift4G	Benign	0.068	T;T;T;T
Polyphen		0.0030	B;B;B;B
Vest4		0.12
MutPred		0.45		Gain of catalytic residue at Q590 (P = 0.0498);Gain of catalytic residue at Q590 (P = 0.0498);Gain of catalytic residue at Q590 (P = 0.0498);Gain of catalytic residue at Q590 (P = 0.0498);
MVP		0.11
MPC		0.028
ClinPred		0.071	T
GERP RS		-4.2
Varity_R		0.082
gMVP		0.049

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: chr19-38055560;