chr19-55644710-C-T

Variant names:

• chr19-55644710-C-T
• rs1982747766
• NM_016535.4:c.139C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016535.4(ZNF581):​c.139C>T​(p.Pro47Ser) 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. 16/22 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: ZNF581 NM_016535.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.46
• Publications: 0 publications found

Genes affected

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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03489408).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016535.4. 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
	ZNF581	NM_016535.4	MANE Select	c.139C>T	p.Pro47Ser	missense	Exon 2 of 2	NP_057619.1	Q9P0T4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF581	ENST00000270451.6	TSL:1 MANE Select	c.139C>T	p.Pro47Ser	missense	Exon 2 of 2	ENSP00000270451.4	Q9P0T4
	ZNF581	ENST00000587252.5	TSL:2	c.139C>T	p.Pro47Ser	missense	Exon 2 of 2	ENSP00000466047.1	Q9P0T4
	ZNF581	ENST00000588537.1	TSL:3	c.139C>T	p.Pro47Ser	missense	Exon 2 of 2	ENSP00000466564.1	Q9P0T4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.072
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.0
DANN	Benign	0.88
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.14	N
PhyloP100		-1.5
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.011
Sift	Benign	1.0	T
Sift4G	Benign	0.44	T
Polyphen		0.0	B
Vest4		0.065
MutPred		0.28		Loss of catalytic residue at P47 (P = 0.0054)
MVP		0.081
MPC		0.68
ClinPred		0.028	T
GERP RS		-0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.019
gMVP		0.17
Mutation Taster		=100/0	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: rs1982747766; hg19: chr19-56156076;