NM_024691.4:c.674A>C

Variant names:

• chr19-57493231-A-C
• NM_024691.4:c.674A>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_024691.4(ZNF419):​c.674A>C​(p.His225Pro) 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 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF419 NM_024691.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.774

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.87

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF419	NM_024691.4	c.674A>C	p.His225Pro	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.674A>C	p.His225Pro	missense_variant	Exon 5 of 5	1	NM_024691.4	ENSP00000221735.7
ENSG00000268107	ENST00000601674.6	n.160+1634A>C		intron_variant	Intron 2 of 5	2		ENSP00000471625.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461874 Hom.: 0 Cov.: 101 AF XY: 0.00 AC XY: 0 AN XY: 727238

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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	20
DANN	Benign	0.83
DEOGEN2	Benign	0.099	.;.;.;.;.;.;T
Eigen	Benign	-0.049
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.77	T;T;T;T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Pathogenic	0.87	D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.069	T
MutationAssessor	Pathogenic	3.3	.;.;.;.;.;.;M
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-8.0	D;D;D;D;D;D;D
REVEL	Uncertain	0.42
Sift	Uncertain	0.017	D;D;D;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D;D;D
Polyphen		0.99, 1.0	.;.;.;.;D;.;D
Vest4		0.49
MutPred		0.82		.;.;.;.;.;.;Gain of methylation at K228 (P = 0.0649);
MVP		0.84
MPC		0.19
ClinPred		0.52	D
GERP RS		2.4
Varity_R		0.67
gMVP		0.38

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: chr19-58004599;