19-57572870-C-T

Variant names:

• chr19-57572870-C-T
• rs529743529
• NM_017879.3:c.1034G>A

Variant summary

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

The NM_017879.3(ZNF416):​c.1034G>A​(p.Cys345Tyr) 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. 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. C345S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF416 NM_017879.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.50
• Publications: 0 publications found

Genes affected

ZNF416 (HGNC:20645): (zinc finger protein 416) 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 act upstream of or within cardiac muscle hypertrophy; negative regulation of cell growth involved in cardiac muscle cell development; and negative regulation of protein phosphorylation. Predicted to be active in nucleus. [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=0.053177).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017879.3. 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
	ZNF416	NM_017879.3	MANE Select	c.1034G>A	p.Cys345Tyr	missense	Exon 4 of 4	NP_060349.1	Q9BWM5
	ZNF416	NM_001353405.2		c.818G>A	p.Cys273Tyr	missense	Exon 3 of 3	NP_001340334.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF416	ENST00000196489.4	TSL:1 MANE Select	c.1034G>A	p.Cys345Tyr	missense	Exon 4 of 4	ENSP00000196489.2	Q9BWM5
	ZNF416	ENST00000896581.1		c.992G>A	p.Cys331Tyr	missense	Exon 4 of 4	ENSP00000566640.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.7
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.27	N
PhyloP100		-3.5
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.87	N
REVEL	Benign	0.043
Sift	Benign	0.26	T
Sift4G	Benign	0.33	T
Polyphen		0.54	P
Vest4		0.063
MutPred		0.45		Gain of phosphorylation at C345 (P = 0.035)
MVP		0.099
MPC		0.69
ClinPred		0.26	T
GERP RS		-3.8
Varity_R		0.036
gMVP		0.064
Mutation Taster		=95/5	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: rs529743529; hg19: chr19-58084238;