19-57701807-C-G

Variant names:

• chr19-57701807-C-G
• rs756405083
• NM_001085384.3:c.1142G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001085384.3(ZNF154):​c.1142G>C​(p.Gly381Ala) 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. 13/22 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. G381V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF154 NM_001085384.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.72
• Publications: 0 publications found

Genes affected

ZNF154 (HGNC:12939): (zinc finger protein 154) This gene encodes a protein that belongs to the zinc finger Kruppel family of transcriptional regulators, whose members are thought to function in normal and abnormal cell growth and differentiation. Hypermethylation of this gene is associated with the recurrence of non muscle invasive bladder cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ENSG00000269026 (HGNC:):

ZNF551 (HGNC:25108): (zinc finger protein 551) 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3365606).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF154	NM_001085384.3	c.1142G>C	p.Gly381Ala	missense_variant	Exon 3 of 3	ENST00000684351.1	NP_001078853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF154	ENST00000684351.1	c.1142G>C	p.Gly381Ala	missense_variant	Exon 3 of 3		NM_001085384.3	ENSP00000507206.1
ENSG00000269026	ENST00000594684.1	c.33+19563C>G		intron_variant	Intron 1 of 2	1		ENSP00000472160.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.068	T
Eigen	Benign	0.18
Eigen_PC	Benign	-0.0062
FATHMM_MKL	Uncertain	0.85	D
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.91	L
PhyloP100		2.7
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Benign	0.11
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.024	D
Polyphen		1.0	D
Vest4		0.31
MutPred		0.38		Gain of MoRF binding (P = 0.1355);
MVP		0.41
MPC		0.51
ClinPred		0.96	D
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.60
gMVP		0.081
Mutation Taster		=65/35	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: rs756405083; hg19: chr19-58213175;