19-57908921-C-G

Variant names:

• chr19-57908921-C-G
• rs553989993
• NM_152475.3:c.1357G>C

Variant summary

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

The NM_152475.3(ZNF417):​c.1357G>C​(p.Val453Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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. V453I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF417 NM_152475.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -8.74

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 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=0.0816904).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF417	NM_152475.3	c.1357G>C	p.Val453Leu	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.1357G>C	p.Val453Leu	missense_variant	Exon 3 of 3	1	NM_152475.3	ENSP00000311319.4
ZNF417	ENST00000595559.1	c.1354G>C	p.Val452Leu	missense_variant	Exon 3 of 3	1		ENSP00000472272.1
ENSG00000269476	ENST00000602124.1	n.34+3139G>C		intron_variant	Intron 3 of 5	3		ENSP00000470782.1
ZNF417	ENST00000594396.1	c.106+3139G>C		intron_variant	Intron 1 of 2	3		ENSP00000472352.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251304 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135824

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461722 Hom.: 0 Cov.: 81 AF XY: 0.00000138 AC XY: 1 AN XY: 727154

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.044
DANN	Benign	0.85
DEOGEN2	Benign	0.0014	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.00091	T
MetaRNN	Benign	0.082	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.17	N;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.25	N;.
REVEL	Benign	0.0020
Sift	Benign	0.61	T;.
Sift4G	Benign	0.52	T;T
Polyphen		0.078	B;.
Vest4		0.059
MutPred		0.35		Loss of MoRF binding (P = 0.0932);.;
MVP		0.25
ClinPred		0.091	T
GERP RS		-3.0
Varity_R		0.034
gMVP		0.019

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: rs553989993; hg19: chr19-58420289;