chr19-57491489-G-T

Variant names:

• chr19-57491489-G-T
• NM_024691.4:c.91G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_024691.4(ZNF419):​c.91G>T​(p.Asp31Tyr) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: ZNF419 NM_024691.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.06
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.839

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024691.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF419	NM_024691.4	MANE Select	c.91G>T	p.Asp31Tyr	missense	Exon 3 of 5	NP_078967.3
	ZNF419	NM_001098491.2		c.94G>T	p.Asp32Tyr	missense	Exon 3 of 5	NP_001091961.1	Q96HQ0-5
	ZNF419	NM_001098492.2		c.55G>T	p.Asp19Tyr	missense	Exon 2 of 4	NP_001091962.1	Q96HQ0-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF419	ENST00000221735.12	TSL:1 MANE Select	c.91G>T	p.Asp31Tyr	missense	Exon 3 of 5	ENSP00000221735.7	Q96HQ0-1
	ZNF419	ENST00000424930.6	TSL:1	c.94G>T	p.Asp32Tyr	missense	Exon 3 of 5	ENSP00000388864.1	Q96HQ0-5
	ZNF419	ENST00000523439.1	TSL:1	n.283G>T		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 60

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0061	T
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.67	T
MutationAssessor	Pathogenic	5.3	H
PhyloP100		3.1
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-8.2	D
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.78		Gain of sheet (P = 0.0221)
MVP		0.40
MPC		0.18
ClinPred		1.0	D
GERP RS		2.8
Varity_R		0.83
gMVP		0.61
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.28		Position offset: 24

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr19-58002857;