chr19-57908857-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 15/20 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

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04458046).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF417	NM_152475.3	c.1421G>C	p.Gly474Ala	missense_variant	Exon 3 of 3	ENST00000312026.6	NP_689688.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF417	ENST00000312026.6	c.1421G>C	p.Gly474Ala	missense_variant	Exon 3 of 3	1	NM_152475.3	ENSP00000311319.4
ZNF417	ENST00000595559.1	c.1418G>C	p.Gly473Ala	missense_variant	Exon 3 of 3	1		ENSP00000472272.1
ENSG00000269476	ENST00000602124.1	n.34+3203G>C		intron_variant	Intron 3 of 5	3		ENSP00000470782.1
ZNF417	ENST00000594396.1	c.106+3203G>C		intron_variant	Intron 1 of 2	3		ENSP00000472352.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 81

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1421G>C (p.G474A) alteration is located in exon 3 (coding exon 3) of the ZNF417 gene. This alteration results from a G to C substitution at nucleotide position 1421, causing the glycine (G) at amino acid position 474 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.025	N
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.045	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.23	N;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.62	N;.
REVEL	Benign	0.020
Sift	Benign	0.41	T;.
Sift4G	Benign	0.46	T;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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-58420225;