19-37564620-T-G

Position:

• chr19-37564620-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016536.5(ZNF571):​c.1808A>C​(p.Gln603Pro) 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. 14/21 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF571 NM_016536.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.830

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28517357).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF571	NM_016536.5	c.1808A>C	p.Gln603Pro	missense_variant	4/4	ENST00000451802.7
ZNF571-AS1	NR_038248.1	n.338-1411T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF571	ENST00000451802.7	c.1808A>C	p.Gln603Pro	missense_variant	4/4	1	NM_016536.5	P1
ZNF571-AS1	ENST00000585578.5	n.210-1411T>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1395014 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 687888

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Nov 09, 2022

The c.1808A>C (p.Q603P) alteration is located in exon 4 (coding exon 3) of the ZNF571 gene. This alteration results from a A to C substitution at nucleotide position 1808, causing the glutamine (Q) at amino acid position 603 to be replaced by a proline (P). 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	Uncertain	0.53
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.0093	T;T;T;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.000040	N
LIST_S2	Benign	0.37	T;.;.;.
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.29	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.3	M;M;M;M
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.9	N;.;N;N
REVEL	Benign	0.21
Sift	Benign	0.12	T;.;T;T
Sift4G	Benign	0.30	T;T;T;T
Polyphen		0.93	P;P;P;P
Vest4		0.35
MutPred		0.31		Gain of glycosylation at T605 (P = 0.0913);Gain of glycosylation at T605 (P = 0.0913);Gain of glycosylation at T605 (P = 0.0913);Gain of glycosylation at T605 (P = 0.0913);
MVP		0.66
MPC		0.19
ClinPred		0.23	T
GERP RS		1.4
Varity_R		0.18
gMVP		0.12

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: chr19-38055522;