Variant 1-40462502-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 NM_023070.3(ZFP69B):c.518T>C(p.Met173Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,788 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: 0.000013 ( 0 hom. )

Consequence

ZFP69B
NM_023070.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00200

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 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=0.064233184).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZFP69B	NM_023070.3 linkuse as main transcript	c.518T>C	p.Met173Thr	missense_variant	5/5	ENST00000361584.5	NP_075558.2
ZFP69B	NM_001369565.1 linkuse as main transcript	c.518T>C	p.Met173Thr	missense_variant	6/6		NP_001356494.1
ZFP69B	XM_005271136.2 linkuse as main transcript	c.521T>C	p.Met174Thr	missense_variant	6/6		XP_005271193.1
ZFP69B	XM_017002147.2 linkuse as main transcript	c.521T>C	p.Met174Thr	missense_variant	6/6		XP_016857636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP69B	ENST00000361584.5 linkuse as main transcript	c.518T>C	p.Met173Thr	missense_variant	5/5	1	NM_023070.3	ENSP00000354547	P1	Q9UJL9-1
ZFP69B	ENST00000484445.5 linkuse as main transcript	c.*36T>C		3_prime_UTR_variant	5/5	1		ENSP00000435907
ZFP69B	ENST00000411995.6 linkuse as main transcript	c.518T>C	p.Met173Thr	missense_variant	6/6	5		ENSP00000399664	P1	Q9UJL9-1
ZFP69B	ENST00000469416.1 linkuse as main transcript	n.1170T>C		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000319

AC:

AN:

251124

Hom.:

AF XY:

0.0000516

AC XY:

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000262

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461788

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000494

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

Jun 29, 2023

The c.518T>C (p.M173T) alteration is located in exon 5 (coding exon 5) of the ZFP69B gene. This alteration results from a T to C substitution at nucleotide position 518, causing the methionine (M) at amino acid position 173 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

-0.55

BayesDel_noAF

Benign

-0.73

CADD

Benign

5.5

DANN

Benign

0.52

DEOGEN2

Benign

0.011

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.000010

LIST_S2

Benign

0.25

.;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.064

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-2.3

N;.

REVEL

Benign

0.074

Sift

Benign

0.096

T;.

Sift4G

Benign

0.57

T;T

Polyphen

0.68

P;P

Vest4

0.12

MutPred

0.32

Gain of phosphorylation at M173 (P = 0.0502);Gain of phosphorylation at M173 (P = 0.0502);

MVP

0.040

MPC

0.11

ClinPred

0.097

GERP RS

-3.6

Varity_R

0.060

gMVP

0.32

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