19-11866592-C-T

Variant names:

• chr19-11866592-C-T
• rs138184942
• NM_001348719.2:c.246C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001348719.2(ZNF439):​c.246C>T​(p.Asn82Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 32)
• Consequence: ZNF439 NM_001348719.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.471
• Publications: 0 publications found

Genes affected

ZNF439 (HGNC:20873): (zinc finger protein 439) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-0.471 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348719.2. 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
	ZNF439	NM_001348719.2	MANE Select	c.246C>T	p.Asn82Asn	synonymous	Exon 3 of 4	NP_001335648.1	A0A804HI69
	ZNF439	NM_001348718.2		c.255C>T	p.Asn85Asn	synonymous	Exon 3 of 4	NP_001335647.1
	ZNF439	NM_152262.3		c.231C>T	p.Asn77Asn	synonymous	Exon 2 of 3	NP_689475.1	Q8NDP4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF439	ENST00000682736.1	MANE Select	c.246C>T	p.Asn82Asn	synonymous	Exon 3 of 4	ENSP00000506930.1	A0A804HI69
	ZNF439	ENST00000304030.2	TSL:1	c.231C>T	p.Asn77Asn	synonymous	Exon 2 of 3	ENSP00000305077.2	Q8NDP4
	ZNF439	ENST00000455282.1	TSL:1	c.-178C>T		5_prime_UTR	Exon 2 of 3	ENSP00000395632.1	A0A0C4DG37

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.61
PhyloP100		-0.47

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

Other links and lift over

dbSNP: rs138184942; hg19: chr19-11977407;