19-57490144-T-G

Variant names:

• chr19-57490144-T-G
• rs11672136
• NM_024691.4:c.34-3T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024691.4(ZNF419):​c.34-3T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 31)
• Consequence: ZNF419 NM_024691.4 splice_region, intron
• Scores: Splicing: ADA: 0.8246
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627
• Publications: 13 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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.34-3T>G		splice_region intron	N/A	NP_078967.3
	ZNF419	NM_001291744.2		c.-138T>G		5_prime_UTR	Exon 2 of 4	NP_001278673.1
	ZNF419	NM_001098491.2		c.34-3T>G		splice_region intron	N/A	NP_001091961.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF419	ENST00000221735.12	TSL:1 MANE Select	c.34-3T>G		splice_region intron	N/A	ENSP00000221735.7
	ZNF419	ENST00000424930.6	TSL:1	c.34-3T>G		splice_region intron	N/A	ENSP00000388864.1
	ZNF419	ENST00000523439.1	TSL:1	n.265-1327T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151832 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151832 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74108

African (AFR) AF: 0.00 AC: 0 AN: 41310

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67974

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 1072

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	16
DANN	Benign	0.56
PhyloP100		-0.63

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.82
dbscSNV1_RF	Benign	0.67
SpliceAI score (max)		0.95		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.46		Position offset: 1
DS_AL_spliceai		0.95		Position offset: 3

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

Other links and lift over

dbSNP: rs11672136; hg19: chr19-58001512;