19-57493021-C-T

Position:

• chr19-57493021-C-T

Variant summary

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

The NM_024691.4(ZNF419):​c.464C>T​(p.Ser155Leu) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF419 NM_024691.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0360

Genes affected

ZNF419 (HGNC:20648): (zinc finger protein 419) 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]

ZNF419 (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=0.16557461).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF419	NM_024691.4	c.464C>T	p.Ser155Leu	missense_variant	5/5	ENST00000221735.12	NP_078967.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF419	ENST00000221735.12	c.464C>T	p.Ser155Leu	missense_variant	5/5	1	NM_024691.4	ENSP00000221735.7
ENSG00000268107	ENST00000601674.6	n.160+1424C>T		intron_variant		2		ENSP00000471625.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 101

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2023

The c.467C>T (p.S156L) alteration is located in exon 5 (coding exon 5) of the ZNF419 gene. This alteration results from a C to T substitution at nucleotide position 467, causing the serine (S) at amino acid position 156 to be replaced by a leucine (L). 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	0.090
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.045	.;.;.;.;.;.;.;T;.
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.019	T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.17	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	.;.;.;.;.;.;.;L;.
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.8	D;D;D;D;D;D;D;D;D
REVEL	Benign	0.029
Sift	Benign	0.17	T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.14	T;T;T;T;T;T;T;T;T
Polyphen		0.99, 0.97	.;.;.;.;D;.;.;D;.
Vest4		0.21
MutPred		0.32		.;.;.;.;.;.;.;Loss of phosphorylation at S155 (P = 0.0457);.;
MVP		0.20
MPC		0.020
ClinPred		0.62	D
GERP RS		0.76
Varity_R		0.14
gMVP		0.031

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: chr19-58004389;