NM_023070.3:c.383A>G

Variant names:

• chr1-40457386-A-G
• rs551315250
• NM_023070.3:c.383A>G

Variant summary

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

The NM_023070.3(ZFP69B):​c.383A>G​(p.Lys128Arg) 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: ZFP69B NM_023070.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.20
• Publications: 0 publications found

Genes affected

ZFP69B (HGNC:28053): (ZFP69 zinc finger protein B) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in Golgi organization. Located in nucleolus. [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=0.11533037).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023070.3. 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
	ZFP69B	NM_023070.3	MANE Select	c.383A>G	p.Lys128Arg	missense	Exon 4 of 5	NP_075558.2	Q9UJL9-1
	ZFP69B	NM_001369565.1		c.383A>G	p.Lys128Arg	missense	Exon 5 of 6	NP_001356494.1	Q9UJL9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP69B	ENST00000361584.5	TSL:1 MANE Select	c.383A>G	p.Lys128Arg	missense	Exon 4 of 5	ENSP00000354547.4	Q9UJL9-1
	ZFP69B	ENST00000484445.5	TSL:1	c.297A>G	p.Glu99Glu	synonymous	Exon 4 of 5	ENSP00000435907.1	E9PS66
	ZFP69B	ENST00000863980.1		c.386A>G	p.Lys129Arg	missense	Exon 5 of 6	ENSP00000534039.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	0.073
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.00071	T
Eigen	Benign	0.0019
Eigen_PC	Benign	0.0044
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.12	T
MetaSVM	Uncertain	-0.076	T
MutationAssessor	Benign	-0.20	N
PhyloP100		2.2
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.084
Sift	Benign	0.41	T
Sift4G	Benign	0.59	T
Polyphen		1.0	D
Vest4		0.10
MutPred		0.37		Loss of methylation at K128 (P = 0.0033)
MVP		0.12
MPC		0.44
ClinPred		0.65	D
GERP RS		3.5
Varity_R		0.049
gMVP		0.034
Mutation Taster		=96/4	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: rs551315250; hg19: chr1-40923058;