Variant 1-40462964-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_023070.3(ZFP69B):c.980G>T(p.Arg327Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000731 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

ZFP69B
NM_023070.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.91

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.12704143).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZFP69B	NM_023070.3 linkuse as main transcript	c.980G>T	p.Arg327Ile	missense_variant	5/5	ENST00000361584.5
ZFP69B	NM_001369565.1 linkuse as main transcript	c.980G>T	p.Arg327Ile	missense_variant	6/6
ZFP69B	XM_005271136.2 linkuse as main transcript	c.983G>T	p.Arg328Ile	missense_variant	6/6
ZFP69B	XM_017002147.2 linkuse as main transcript	c.983G>T	p.Arg328Ile	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFP69B	ENST00000361584.5 linkuse as main transcript	c.980G>T	p.Arg327Ile	missense_variant	5/5	1	NM_023070.3	P1	Q9UJL9-1
ZFP69B	ENST00000484445.5 linkuse as main transcript	c.*498G>T		3_prime_UTR_variant	5/5	1
ZFP69B	ENST00000411995.6 linkuse as main transcript	c.980G>T	p.Arg327Ile	missense_variant	6/6	5		P1	Q9UJL9-1
ZFP69B	ENST00000469416.1 linkuse as main transcript	n.1632G>T		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.000361

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000479

GnomAD3 exomes

AF:

0.0000597

AC:

AN:

251212

Hom.:

AF XY:

0.0000516

AC XY:

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.000862

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000431

AC:

AN:

1461850

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00170

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.000361

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.000196

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:

0.000479

Alfa

AF:

0.000291

Hom.:

Bravo

AF:

0.000340

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000576

AC:

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

Dec 03, 2021

The c.980G>T (p.R327I) alteration is located in exon 5 (coding exon 5) of the ZFP69B gene. This alteration results from a G to T substitution at nucleotide position 980, causing the arginine (R) at amino acid position 327 to be replaced by an isoleucine (I). 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

Pathogenic

0.67

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.055

T;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Benign

0.00044

M_CAP

Benign

0.014

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-7.6

D;.

REVEL

Benign

0.20

Sift

Uncertain

0.020

D;.

Sift4G

Uncertain

0.044

D;D

Polyphen

1.0

D;D

Vest4

0.45

MVP

0.28

MPC

0.65

ClinPred

0.39

GERP RS

3.1

Varity_R

0.52

gMVP

0.094

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