rs754882375

Variant names:

• chr19-57493141-C-A
• rs754882375
• NM_024691.4:c.584C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-57493141-C-A
• chr19-57493141-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.584C>A​(p.Ala195Asp) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF419 NM_024691.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.996

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]

ENSG00000268107 (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=0.068721354).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF419	NM_024691.4	c.584C>A	p.Ala195Asp	missense_variant	Exon 5 of 5	ENST00000221735.12	NP_078967.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF419	ENST00000221735.12	c.584C>A	p.Ala195Asp	missense_variant	Exon 5 of 5	1	NM_024691.4	ENSP00000221735.7
ENSG00000268107	ENST00000601674.6	n.160+1544C>A		intron_variant	Intron 2 of 5	2		ENSP00000471625.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 101

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.040	.;.;.;.;.;.;T;.
Eigen	Benign	-0.79
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.014	T;T;T;T;T;T;T;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.069	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	.;.;.;.;.;.;M;.
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.6	D;D;D;D;D;D;D;D
REVEL	Benign	0.063
Sift	Benign	0.30	T;T;T;T;D;T;T;T
Sift4G	Benign	0.30	T;T;T;T;T;T;T;T
Polyphen		0.99, 0.94	.;.;.;.;D;.;P;.
Vest4		0.16
MutPred		0.22		.;.;.;.;.;.;Gain of relative solvent accessibility (P = 0.0249);.;
MVP		0.15
MPC		0.051
ClinPred		0.32	T
GERP RS		-1.8
Varity_R		0.23
gMVP		0.029

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: rs754882375; hg19: chr19-58004509;