Variant chr1-40457412-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000361584.5(ZFP69B):c.409A>G(p.Arg137Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZFP69B
ENST00000361584.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0450

Variant links:

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]

ZFP69B links:

ZFP69B (HGNC:):

ZFP69B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.061213225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP69B	NM_023070.3 linkuse as main transcript	c.409A>G	p.Arg137Gly	missense_variant	4/5	ENST00000361584.5	NP_075558.2	Q9UJL9-1
ZFP69B	NM_001369565.1 linkuse as main transcript	c.409A>G	p.Arg137Gly	missense_variant	5/6		NP_001356494.1
ZFP69B	XM_005271136.2 linkuse as main transcript	c.412A>G	p.Arg138Gly	missense_variant	5/6		XP_005271193.1
ZFP69B	XM_017002147.2 linkuse as main transcript	c.412A>G	p.Arg138Gly	missense_variant	5/6		XP_016857636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZFP69B	ENST00000361584.5 linkuse as main transcript	c.409A>G	p.Arg137Gly	missense_variant	4/5	1	NM_023070.3	ENSP00000354547.4	Q9UJL9-1
ZFP69B	ENST00000484445.5 linkuse as main transcript	c.323A>G	p.Glu108Gly	missense_variant	4/5	1		ENSP00000435907.1	E9PS66
ZFP69B	ENST00000411995.6 linkuse as main transcript	c.409A>G	p.Arg137Gly	missense_variant	5/6	5		ENSP00000399664.2	Q9UJL9-1
ZFP69B	ENST00000469416.1 linkuse as main transcript	n.1061A>G		non_coding_transcript_exon_variant	4/5	2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461782

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152078

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 20, 2024

The c.409A>G (p.R137G) 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 409, causing the arginine (R) at amino acid position 137 to be replaced by a glycine (G). 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

0.085

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.94

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0060

LIST_S2

Benign

0.36

M_CAP

Benign

0.00088

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.94

MutationTaster

Benign

1.0

N;N;N;N

PROVEAN

Benign

-0.62

REVEL

Benign

0.071

Sift

Uncertain

0.013

Sift4G

Pathogenic

0.0

Vest4

0.13

MutPred

0.26

Loss of solvent accessibility (P = 0.0387);

MVP

0.15

ClinPred

0.086

GERP RS

-1.9

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over