19-37564974-C-A

Variant names:

• chr19-37564974-C-A
• rs151146788
• NM_016536.5:c.1454G>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.1454G>T​(p.Arg485Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R485H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF571 NM_016536.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• 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=0.07772094).

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.1454G>T	p.Arg485Leu	missense	Exon 4 of 4	NP_057620.3
	ZNF571	NM_001290314.2		c.1454G>T	p.Arg485Leu	missense	Exon 5 of 5	NP_001277243.1	Q7Z3V5
	ZNF571	NM_001321272.2		c.1454G>T	p.Arg485Leu	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.1454G>T	p.Arg485Leu	missense	Exon 4 of 4	ENSP00000392638.1	Q7Z3V5
	ZNF571	ENST00000593133.5	TSL:1	c.1454G>T	p.Arg485Leu	missense	Exon 4 of 4	ENSP00000467572.1	Q7Z3V5
	ZNF571-AS1	ENST00000585578.5	TSL:1	n.210-1057C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461538 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727068

African (AFR) AF: 0.0000299 AC: 1 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111848

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.0074	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.000070	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.68	N
PhyloP100		-1.3
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.026
Sift	Benign	0.67	T
Sift4G	Benign	0.49	T
Polyphen		0.016	B
Vest4		0.16
MutPred		0.48		Loss of MoRF binding (P = 0.011)
MVP		0.13
MPC		0.18
ClinPred		0.55	D
GERP RS		0.77
Varity_R		0.058
gMVP		0.056
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

dbSNP: rs151146788; hg19: chr19-38055876;