NM_001348719.2:c.569C>T

Variant names:

• chr19-11867623-C-T
• rs373484496
• NM_001348719.2:c.569C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001348719.2(ZNF439):​c.569C>T​(p.Pro190Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,613,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: ZNF439 NM_001348719.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.36
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09282896).

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.569C>T	p.Pro190Leu	missense	Exon 4 of 4	NP_001335648.1	A0A804HI69
	ZNF439	NM_001348718.2		c.578C>T	p.Pro193Leu	missense	Exon 4 of 4	NP_001335647.1
	ZNF439	NM_152262.3		c.554C>T	p.Pro185Leu	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.569C>T	p.Pro190Leu	missense	Exon 4 of 4	ENSP00000506930.1	A0A804HI69
	ZNF439	ENST00000304030.2	TSL:1	c.554C>T	p.Pro185Leu	missense	Exon 3 of 3	ENSP00000305077.2	Q8NDP4
	ZNF439	ENST00000455282.1	TSL:1	c.146C>T	p.Pro49Leu	missense	Exon 3 of 3	ENSP00000395632.1	A0A0C4DG37

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251338 AF XY: 0.00000736

Gnomad AFR exome AF: 0.0000615

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: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000752 AC: 11 AN: 1461802 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727196

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

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

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111980

Other (OTH) AF: 0.0000166 AC: 1 AN: 60388

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152130 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74326

African (AFR) AF: 0.0000724 AC: 3 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15272

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000165 AC: 2

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	0.13
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	6.7
DANN	Benign	0.95
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.062	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.4
PrimateAI	Benign	0.22	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Benign	0.037
Sift	Benign	0.062	T
Sift4G	Uncertain	0.039	D
Polyphen		0.081	B
Vest4		0.10
MVP		0.28
MPC		0.054
ClinPred		0.097	T
GERP RS		0.57
Varity_R		0.11
gMVP		0.012
Mutation Taster		=94/6	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: rs373484496; hg19: chr19-11978438; COSMIC: COSV58308496; COSMIC: COSV58308496;