rs543687016

Variant names:

• chr19-52384127-C-A
• rs543687016
• NM_001145434.2:c.547C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-52384127-C-A
• chr19-52384127-C-T

Variant summary

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

The NM_001145434.2(ZNF880):​c.547C>A​(p.Pro183Thr) 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. 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. P183S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF880 NM_001145434.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.591

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

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=0.11964321).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF880	NM_001145434.2	c.547C>A	p.Pro183Thr	missense_variant	Exon 4 of 4	ENST00000422689.3	NP_001138906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF880	ENST00000422689.3	c.547C>A	p.Pro183Thr	missense_variant	Exon 4 of 4	2	NM_001145434.2	ENSP00000406318.2
ZNF880	ENST00000424032.6	c.*289C>A		downstream_gene_variant		4		ENSP00000414470.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000434 AC: 1 AN: 230524 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 124994

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000597

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	2.2
DANN	Benign	0.43
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.14	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.2	M
PrimateAI	Benign	0.22	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.044
Sift	Benign	0.058	T
Sift4G	Uncertain	0.039	D
Polyphen		0.89	P
Vest4		0.14
MutPred		0.43		Loss of catalytic residue at P183 (P = 0.0055);
MVP		0.17
MPC		0.049
ClinPred		0.33	T
GERP RS		1.7
Varity_R		0.081
gMVP		0.017

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

LitVar

Other links and lift over

dbSNP: rs543687016; hg19: chr19-52887380;