NM_001144068.2:c.778A>G

Variant names:

• chr19-57473843-T-C
• rs2089248005
• NM_001144068.2:c.778A>G

Variant summary

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

The NM_001144068.2(ZNF772):​c.778A>G​(p.Lys260Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ZNF772 NM_001144068.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00
• Publications: 0 publications found

Genes affected

ZNF772 (HGNC:33106): (zinc finger protein 772) 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]

ENSG00000268163 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144068.2. 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
	ZNF772	NM_001144068.2	MANE Select	c.778A>G	p.Lys260Glu	missense	Exon 4 of 4	NP_001137540.1	Q68DY9-3
	ZNF772	NM_001024596.3		c.901A>G	p.Lys301Glu	missense	Exon 5 of 5	NP_001019767.1	Q68DY9-1
	ZNF772	NM_001439216.1		c.739A>G	p.Lys247Glu	missense	Exon 3 of 3	NP_001426145.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF772	ENST00000356584.8	TSL:2 MANE Select	c.778A>G	p.Lys260Glu	missense	Exon 4 of 4	ENSP00000348992.3	Q68DY9-3
	ZNF772	ENST00000343280.8	TSL:1	c.901A>G	p.Lys301Glu	missense	Exon 5 of 5	ENSP00000341165.4	Q68DY9-1
	ZNF772	ENST00000427512.6	TSL:1	c.565A>G	p.Lys189Glu	missense	Exon 2 of 2	ENSP00000395967.2	Q68DY9-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152204 Hom.: 0 Cov.: 33

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461840 Hom.: 0 Cov.: 45 AF XY: 0.00000413 AC XY: 3 AN XY: 727222

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111966

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152204 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74358

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15278

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

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	0.89
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0043	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.0
PrimateAI	Pathogenic	0.80	D
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.18
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.98	D
Vest4		0.36
MutPred		0.48		Loss of methylation at K301 (P = 0.0029)
MVP		0.59
MPC		0.96
ClinPred		0.97	D
GERP RS		3.5
Varity_R		0.40
gMVP		0.10
Mutation Taster		=58/42	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: rs2089248005; hg19: chr19-57985211;