NM_152475.3:c.1421G>C

Variant names:

• chr19-57908857-C-G
• NM_152475.3:c.1421G>C

Variant summary

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

The NM_152475.3(ZNF417):​c.1421G>C​(p.Gly474Ala) 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: ZNF417 NM_152475.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.99
• Publications: 0 publications found

Genes affected

ZNF417 (HGNC:20646): (zinc finger protein 417) 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]

ENSG00000269476 (HGNC:):

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=0.04458046).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152475.3. 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
	ZNF417	NM_152475.3	MANE Select	c.1421G>C	p.Gly474Ala	missense	Exon 3 of 3	NP_689688.2	Q8TAU3-1
	ZNF417	NM_001297734.2		c.1418G>C	p.Gly473Ala	missense	Exon 3 of 3	NP_001284663.1	M0R230

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF417	ENST00000312026.6	TSL:1 MANE Select	c.1421G>C	p.Gly474Ala	missense	Exon 3 of 3	ENSP00000311319.4	Q8TAU3-1
	ZNF417	ENST00000595559.1	TSL:1	c.1418G>C	p.Gly473Ala	missense	Exon 3 of 3	ENSP00000472272.1	M0R230
	ENSG00000269476	ENST00000602124.1	TSL:3	n.34+3203G>C		intron	N/A	ENSP00000470782.1	M0QZU9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 81

GnomAD4 genome Cov.: 32

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	0.18
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.25
DANN	Benign	0.96
DEOGEN2	Benign	0.00053	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.025	N
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.23	N
PhyloP100		-3.0
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.62	N
REVEL	Benign	0.020
Sift	Benign	0.41	T
Sift4G	Benign	0.46	T
Polyphen		0.021	B
Vest4		0.045
MutPred		0.40		Gain of ubiquitination at K471 (P = 0.0662)
MVP		0.25
ClinPred		0.080	T
GERP RS		-0.12
Varity_R		0.026
gMVP		0.0077
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

hg19: chr19-58420225;