NM_001320179.2:c.763A>G

Variant names:

• chr1-40495241-A-G
• rs1645618333
• NM_001320179.2:c.763A>G

Variant summary

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

The NM_001320179.2(ZFP69):​c.763A>G​(p.Lys255Glu) variant causes a missense 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFP69 NM_001320179.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.10
• Publications: 0 publications found

Genes affected

ZFP69 (HGNC:24708): (ZFP69 zinc finger protein) 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 and regulation of lipid metabolic process. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

EXO5-DT (HGNC:55647): (EXO5 divergent transcript)

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=0.0717518).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320179.2. 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
	ZFP69	NM_001320179.2	MANE Select	c.763A>G	p.Lys255Glu	missense	Exon 6 of 6	NP_001307108.1	Q49AA0
	ZFP69	NM_001320178.2		c.766A>G	p.Lys256Glu	missense	Exon 6 of 6	NP_001307107.1
	ZFP69	NM_198494.3		c.763A>G	p.Lys255Glu	missense	Exon 6 of 6	NP_940896.2	Q49AA0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP69	ENST00000372706.6	TSL:1 MANE Select	c.763A>G	p.Lys255Glu	missense	Exon 6 of 6	ENSP00000361791.1	Q49AA0
	ZFP69	ENST00000853135.1		c.766A>G	p.Lys256Glu	missense	Exon 6 of 6	ENSP00000523194.1
	ZFP69	ENST00000853137.1		c.766A>G	p.Lys256Glu	missense	Exon 6 of 6	ENSP00000523196.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Benign	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.0066	N
LIST_S2	Benign	0.0034	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.1
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.11
Sift	Benign	0.54	T
Sift4G	Benign	0.54	T
Polyphen		0.19	B
Vest4		0.26
MutPred		0.40		Loss of ubiquitination at K255 (P = 0.0224)
MVP		0.16
MPC		0.46
ClinPred		0.71	D
GERP RS		4.4
Varity_R		0.21
gMVP		0.10
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: rs1645618333; hg19: chr1-40960913;