19-52384061-T-C

Variant names:

• chr19-52384061-T-C
• rs1568664601
• NM_001145434.2:c.481T>C

Variant summary

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

The NM_001145434.2(ZNF880):​c.481T>C​(p.Tyr161His) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF880 NM_001145434.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.49
• Publications: 0 publications found

Genes affected

ZNF880 (HGNC:37249): (zinc finger protein 880) 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. Predicted to be active in nucleus. [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=0.18593428).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145434.2. 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
	ZNF880	NM_001145434.2	MANE Select	c.481T>C	p.Tyr161His	missense	Exon 4 of 4	NP_001138906.1	Q6PDB4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF880	ENST00000422689.3	TSL:2 MANE Select	c.481T>C	p.Tyr161His	missense	Exon 4 of 4	ENSP00000406318.2	Q6PDB4-1
	ZNF880	ENST00000906539.1		c.481T>C	p.Tyr161His	missense	Exon 4 of 5	ENSP00000576598.1
	ZNF880	ENST00000945824.1		c.469T>C	p.Tyr157His	missense	Exon 4 of 4	ENSP00000615883.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 33

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	0.11
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.6
DANN	Benign	0.21
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.022	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-1.5
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.19
Sift	Benign	0.33	T
Sift4G	Benign	0.46	T
Polyphen		0.99	D
Vest4		0.059
MutPred		0.64		Loss of stability (P = 0.02)
MVP		0.076
MPC		0.054
ClinPred		0.17	T
GERP RS		-2.4
Varity_R		0.054
gMVP		0.034
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: rs1568664601; hg19: chr19-52887314;