NM_024691.4:c.334G>A

Variant names:

• chr19-57492891-G-A
• NM_024691.4:c.334G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024691.4(ZNF419):​c.334G>A​(p.Glu112Lys) 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 1,461,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF419 NM_024691.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514

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 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=0.059259593).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF419	NM_024691.4	c.334G>A	p.Glu112Lys	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.334G>A	p.Glu112Lys	missense_variant	Exon 5 of 5	1	NM_024691.4	ENSP00000221735.7
ENSG00000268107	ENST00000601674.6	n.160+1294G>A		intron_variant	Intron 2 of 5	2		ENSP00000471625.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461726 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727172

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.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.39
DANN	Benign	0.59
DEOGEN2	Benign	0.0045	.;.;.;.;.;.;.;.;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.45	T;T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.059	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.28	.;.;.;.;.;.;.;.;N;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.64	N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.016
Sift	Benign	0.41	T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.60	T;T;D;T;T;T;T;T;T;T
Polyphen		0.011, 0.012	.;.;.;.;.;B;.;.;B;.
Vest4		0.22
MutPred		0.44		.;.;.;.;.;.;.;.;Gain of methylation at E112 (P = 0.0061);.;
MVP		0.16
MPC		0.021
ClinPred		0.023	T
GERP RS		0.074
Varity_R		0.035
gMVP		0.045

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr19-58004259;