chr19-55642692-C-T

Variant names:

• chr19-55642692-C-T
• rs1982595028
• NM_207115.2:c.184C>T

Variant summary

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

The NM_207115.2(ZNF580):​c.184C>T​(p.Pro62Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000339 in 1,474,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: ZNF580 NM_207115.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.85
• Publications: 0 publications found

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

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=0.2111417).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207115.2. 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
	ZNF580	NM_207115.2	MANE Select	c.184C>T	p.Pro62Ser	missense	Exon 2 of 2	NP_996998.1	Q9UK33
	ZNF580	NM_001163423.2		c.184C>T	p.Pro62Ser	missense	Exon 2 of 2	NP_001156895.1	Q9UK33
	ZNF580	NM_016202.2		c.184C>T	p.Pro62Ser	missense	Exon 1 of 1	NP_057286.1	Q9UK33

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF580	ENST00000325333.10	TSL:1 MANE Select	c.184C>T	p.Pro62Ser	missense	Exon 2 of 2	ENSP00000320050.4	Q9UK33
	ZNF580	ENST00000543039.2	TSL:6	c.184C>T	p.Pro62Ser	missense	Exon 1 of 1	ENSP00000443957.1	Q9UK33
	ZNF580	ENST00000545125.1	TSL:3	c.184C>T	p.Pro62Ser	missense	Exon 2 of 2	ENSP00000446126.1	Q9UK33

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152126 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000302 AC: 4 AN: 1322390 Hom.: 0 Cov.: 36 AF XY: 0.00000309 AC XY: 2 AN XY: 648282

African (AFR) AF: 0.00 AC: 0 AN: 26704

American (AMR) AF: 0.00 AC: 0 AN: 24132

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20992

East Asian (EAS) AF: 0.00 AC: 0 AN: 31592

South Asian (SAS) AF: 0.00 AC: 0 AN: 71742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43888

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4558

European-Non Finnish (NFE) AF: 0.00000383 AC: 4 AN: 1044456

Other (OTH) AF: 0.00 AC: 0 AN: 54326

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152126 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74308

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

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	Pathogenic	0.78
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.085
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.68	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.8
PrimateAI	Pathogenic	0.93	D
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.10
Sift	Uncertain	0.011	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.11	B
Vest4		0.13
MutPred		0.41		Gain of catalytic residue at P62 (P = 0.0244)
MVP		0.12
MPC		1.6
ClinPred		0.88	D
GERP RS		4.1
Varity_R		0.30
gMVP		0.41
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1982595028; hg19: chr19-56154058;