Variant 1-40457419-T-C 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.416T>C(p.Ile139Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZFP69B
ENST00000361584.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.01

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=0.043082982).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP69B	NM_023070.3 linkuse as main transcript	c.416T>C	p.Ile139Thr	missense_variant	4/5	ENST00000361584.5	NP_075558.2	Q9UJL9-1
ZFP69B	NM_001369565.1 linkuse as main transcript	c.416T>C	p.Ile139Thr	missense_variant	5/6		NP_001356494.1
ZFP69B	XM_005271136.2 linkuse as main transcript	c.419T>C	p.Ile140Thr	missense_variant	5/6		XP_005271193.1
ZFP69B	XM_017002147.2 linkuse as main transcript	c.419T>C	p.Ile140Thr	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.416T>C	p.Ile139Thr	missense_variant	4/5	1	NM_023070.3	ENSP00000354547.4	Q9UJL9-1
ZFP69B	ENST00000484445.5 linkuse as main transcript	c.330T>C	p.Tyr110Tyr	synonymous_variant	4/5	1		ENSP00000435907.1	E9PS66
ZFP69B	ENST00000411995.6 linkuse as main transcript	c.416T>C	p.Ile139Thr	missense_variant	5/6	5		ENSP00000399664.2	Q9UJL9-1
ZFP69B	ENST00000469416.1 linkuse as main transcript	n.1068T>C		non_coding_transcript_exon_variant	4/5	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251376

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

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

Nov 02, 2023

The c.416T>C (p.I139T) alteration is located in exon 4 (coding exon 4) of the ZFP69B gene. This alteration results from a T to C substitution at nucleotide position 416, causing the isoleucine (I) at amino acid position 139 to be replaced by a threonine (T). 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

0.11

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.51

DANN

Benign

0.28

DEOGEN2

Benign

0.0054

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.12

.;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.043

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.98

L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.8

N;.

REVEL

Benign

0.0060

Sift

Benign

0.66

T;.

Sift4G

Benign

0.53

T;T

Polyphen

0.094

B;B

Vest4

0.11

MutPred

0.38

Gain of phosphorylation at I139 (P = 0.0226);Gain of phosphorylation at I139 (P = 0.0226);

MVP

0.040

MPC

0.14

ClinPred

0.032

GERP RS

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.030

gMVP

0.026

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