19-37565064-G-A

Variant names:

• chr19-37565064-G-A
• NM_016536.5:c.1364C>T

Variant summary

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

The NM_016536.5(ZNF571):​c.1364C>T​(p.Ala455Val) 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. 14/22 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: 0.0450
• Publications: 0 publications found

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

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=0.21591267).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016536.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF571	NM_016536.5	MANE Select	c.1364C>T	p.Ala455Val	missense	Exon 4 of 4	NP_057620.3
	ZNF571	NM_001290314.2		c.1364C>T	p.Ala455Val	missense	Exon 5 of 5	NP_001277243.1	Q7Z3V5
	ZNF571	NM_001321272.2		c.1364C>T	p.Ala455Val	missense	Exon 4 of 4	NP_001308201.1	Q7Z3V5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF571	ENST00000451802.7	TSL:1 MANE Select	c.1364C>T	p.Ala455Val	missense	Exon 4 of 4	ENSP00000392638.1	Q7Z3V5
	ZNF571	ENST00000593133.5	TSL:1	c.1364C>T	p.Ala455Val	missense	Exon 4 of 4	ENSP00000467572.1	Q7Z3V5
	ZNF571-AS1	ENST00000585578.5	TSL:1	n.210-967G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.084
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.000070	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.045
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.11
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.97	D
Vest4		0.068
MutPred		0.66		Loss of ubiquitination at K450 (P = 0.1072)
MVP		0.26
MPC		0.037
ClinPred		0.51	D
GERP RS		3.6
Varity_R		0.25
gMVP		0.0094
Mutation Taster		=98/2	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

hg19: chr19-38055966;