chr19-55642648-C-T

Position:

• chr19-55642648-C-T

Variant summary

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

The NM_207115.2(ZNF580):​c.140C>T​(p.Pro47Leu) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF580 NM_207115.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.38

Genes affected

ZNF580 (HGNC:29473): (zinc finger protein 580) Enables sequence-specific double-stranded DNA binding activity. Involved in several processes, including cellular response to hydrogen peroxide; positive regulation of cell migration; and positive regulation of interleukin-8 production. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF581 (HGNC:25017): (zinc finger protein 581) Predicted to enable DNA-binding transcription factor activity 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 located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CCDC106 (HGNC:30181): (coiled-coil domain containing 106) 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=0.1155633).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF580	NM_207115.2	c.140C>T	p.Pro47Leu	missense_variant	2/2	ENST00000325333.10	NP_996998.1
ZNF580	NM_001163423.2	c.140C>T	p.Pro47Leu	missense_variant	2/2		NP_001156895.1
ZNF580	NM_016202.2	c.140C>T	p.Pro47Leu	missense_variant	1/1		NP_057286.1
ZNF581	XM_017026867.2	c.-19-1905C>T		intron_variant			XP_016882356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF580	ENST00000325333.10	c.140C>T	p.Pro47Leu	missense_variant	2/2	1	NM_207115.2	ENSP00000320050.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

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

Apr 18, 2023

The c.140C>T (p.P47L) alteration is located in exon 1 (coding exon 1) of the ZNF580 gene. This alteration results from a C to T substitution at nucleotide position 140, causing the proline (P) at amino acid position 47 to be replaced by a leucine (L). 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	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.093	T;T;T;.;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.69	T;.;.;T;T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.90	.;L;L;.;L
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.3	.;N;N;.;N
REVEL	Benign	0.051
Sift	Benign	0.10	.;T;T;.;T
Sift4G	Uncertain	0.013	D;D;D;D;D
Polyphen		0.0020	.;B;B;.;B
Vest4		0.10, 0.10
MutPred		0.25		Loss of catalytic residue at P47 (P = 0.0148);Loss of catalytic residue at P47 (P = 0.0148);Loss of catalytic residue at P47 (P = 0.0148);Loss of catalytic residue at P47 (P = 0.0148);Loss of catalytic residue at P47 (P = 0.0148);
MVP		0.043
MPC		0.93
ClinPred		0.54	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.39

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: chr19-56154014;