19-11867670-A-G

Variant names:

• chr19-11867670-A-G
• rs772083513
• NM_001348719.2:c.616A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001348719.2(ZNF439):​c.616A>G​(p.Ile206Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I206L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: ZNF439 NM_001348719.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.825
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03472361).

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.616A>G	p.Ile206Val	missense	Exon 4 of 4	NP_001335648.1	A0A804HI69
	ZNF439	NM_001348718.2		c.625A>G	p.Ile209Val	missense	Exon 4 of 4	NP_001335647.1
	ZNF439	NM_152262.3		c.601A>G	p.Ile201Val	missense	Exon 3 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.616A>G	p.Ile206Val	missense	Exon 4 of 4	ENSP00000506930.1	A0A804HI69
	ZNF439	ENST00000304030.2	TSL:1	c.601A>G	p.Ile201Val	missense	Exon 3 of 3	ENSP00000305077.2	Q8NDP4
	ZNF439	ENST00000455282.1	TSL:1	c.193A>G	p.Ile65Val	missense	Exon 3 of 3	ENSP00000395632.1	A0A0C4DG37

Frequencies

GnomAD3 genomes AF: 0.0000919 AC: 14 AN: 152260 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000338

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000318 AC: 8 AN: 251324 AF XY: 0.0000147

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000889 AC: 13 AN: 1461818 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6 AN XY: 727212

African (AFR) AF: 0.000149 AC: 5 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111988

Other (OTH) AF: 0.0000497 AC: 3 AN: 60390

GnomAD4 genome AF: 0.0000919 AC: 14 AN: 152260 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74396

African (AFR) AF: 0.000338 AC: 14 AN: 41470

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68050

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000761 Hom.: 0

Bravo AF: 0.000110

ExAC AF: 0.0000247 AC: 3

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	Benign	0.11
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.15
DANN	Benign	0.33
DEOGEN2	Benign	0.0083	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.023	T
M_CAP	Benign	0.00088	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.79	N
PhyloP100		-0.82
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.011
Sift	Benign	0.14	T
Sift4G	Benign	0.078	T
Polyphen		0.0050	B
Vest4		0.057
MVP		0.19
MPC		0.046
ClinPred		0.010	T
GERP RS		0.12
Varity_R		0.030
gMVP		0.0080
Mutation Taster		=100/0	polymorphism

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: rs772083513; hg19: chr19-11978485;