1-40457386-A-G

Position:

• chr1-40457386-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11533037).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP69B	NM_023070.3	c.383A>G	p.Lys128Arg	missense_variant	4/5	ENST00000361584.5	NP_075558.2
ZFP69B	NM_001369565.1	c.383A>G	p.Lys128Arg	missense_variant	5/6		NP_001356494.1
ZFP69B	XM_005271136.2	c.386A>G	p.Lys129Arg	missense_variant	5/6		XP_005271193.1
ZFP69B	XM_017002147.2	c.386A>G	p.Lys129Arg	missense_variant	5/6		XP_016857636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP69B	ENST00000361584.5	c.383A>G	p.Lys128Arg	missense_variant	4/5	1	NM_023070.3	ENSP00000354547	P1
ZFP69B	ENST00000484445.5	c.297A>G	p.Glu99=	synonymous_variant	4/5	1		ENSP00000435907
ZFP69B	ENST00000411995.6	c.383A>G	p.Lys128Arg	missense_variant	5/6	5		ENSP00000399664	P1
ZFP69B	ENST00000469416.1	n.1035A>G		non_coding_transcript_exon_variant	4/5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 09, 2023

The c.383A>G (p.K128R) alteration is located in exon 4 (coding exon 4) of the ZFP69B gene. This alteration results from a A to G substitution at nucleotide position 383, causing the lysine (K) at amino acid position 128 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;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;T
MetaSVM	Uncertain	-0.076	T
MutationAssessor	Benign	-0.20	N;N
MutationTaster	Benign	1.0	D;D;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.44	N;N
REVEL	Benign	0.084
Sift	Benign	0.41	T;T
Sift4G	Benign	0.59	T;T
Polyphen		1.0	D;D
Vest4		0.10
MutPred		0.37		Loss of methylation at K128 (P = 0.0033);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-40923058;