rs193920918

Positions:

• chr19-57491471-G-T

Variant summary

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

The NM_024691.4(ZNF419):​c.73G>T​(p.Gly25Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 30)
• Consequence: ZNF419 NM_024691.4 missense, splice_region
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.81

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF419	NM_024691.4	c.73G>T	p.Gly25Cys	missense_variant, splice_region_variant	3/5	ENST00000221735.12	NP_078967.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF419	ENST00000221735.12	c.73G>T	p.Gly25Cys	missense_variant, splice_region_variant	3/5	1	NM_024691.4	ENSP00000221735.7
ENSG00000268107	ENST00000601674.6	n.34G>T		splice_region_variant, non_coding_transcript_exon_variant	2/6	2		ENSP00000471625.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 60

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	.;.;.;.;.;.;.;.;.;.;.;T;.;.
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.0083	T;T;T;T;T;T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.0033	T
MetaRNN	Uncertain	0.47	T;T;T;T;T;T;T;T;D;T;T;D;T;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	.;.;.;.;.;.;.;.;.;.;.;M;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.3	D;D;D;D;D;D;D;D;D;D;D;D;D;D
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen		1.0	.;.;.;.;.;.;.;D;.;.;.;D;.;.
Vest4		0.47
MutPred		0.57		.;.;.;.;.;.;.;.;Gain of sheet (P = 0.039);.;.;Gain of sheet (P = 0.039);.;Gain of sheet (P = 0.039);
MVP		0.36
MPC		0.15
ClinPred		0.97	D
GERP RS		2.8
Varity_R		0.49
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs193920918; hg19: chr19-58002839;