rs1436312371

Variant names:

• chr19-57493283-T-A
• rs1436312371
• NM_024691.4:c.726T>A

Your query was ambiguous. Multiple possible variants found:

• chr19-57493283-T-A
• chr19-57493283-T-C
• chr19-57493283-T-G

Variant summary

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

The NM_024691.4(ZNF419):​c.726T>A​(p.Asp242Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF419 NM_024691.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.25

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=0.045420438).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF419	NM_024691.4	c.726T>A	p.Asp242Glu	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.726T>A	p.Asp242Glu	missense_variant	Exon 5 of 5	1	NM_024691.4	ENSP00000221735.7
ENSG00000268107	ENST00000601674.6	n.160+1686T>A		intron_variant	Intron 2 of 5	2		ENSP00000471625.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251348 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135908

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461890 Hom.: 0 Cov.: 101 AF XY: 0.00000275 AC XY: 2 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

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: 0.00

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	Pathogenic	0.75
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.53
DEOGEN2	Benign	0.0036	.;.;.;.;.;.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0073	N
LIST_S2	Benign	0.50	T;T;T;T;T;T;T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.045	T;T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.90	.;.;.;.;.;.;L
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.87	N;N;N;N;N;N;N
REVEL	Benign	0.0050
Sift	Benign	0.27	T;T;T;T;T;T;T
Sift4G	Benign	0.35	T;T;T;T;T;T;T
Polyphen		0.018, 0.0020	.;.;.;.;B;.;B
Vest4		0.089
MutPred		0.45		.;.;.;.;.;.;Gain of ubiquitination at K238 (P = 0.115);
MVP		0.055
MPC		0.020
ClinPred		0.040	T
GERP RS		-2.3
Varity_R		0.039
gMVP		0.021

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: rs1436312371; hg19: chr19-58004651;