Genetic Variant ZFP69B:p.Ser149Gly (chr1-40462429-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_023070.3(ZFP69B):c.445A>G(p.Ser149Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00005 in 1,580,500 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

ZFP69B
NM_023070.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.676

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:

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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=0.0640991).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP69B	NM_023070.3 link	c.445A>G	p.Ser149Gly	missense_variant	Exon 5 of 5	ENST00000361584.5	NP_075558.2	Q9UJL9-1
ZFP69B	NM_001369565.1 link	c.445A>G	p.Ser149Gly	missense_variant	Exon 6 of 6		NP_001356494.1
ZFP69B	XM_005271136.2 link	c.448A>G	p.Ser150Gly	missense_variant	Exon 6 of 6		XP_005271193.1
ZFP69B	XM_017002147.2 link	c.448A>G	p.Ser150Gly	missense_variant	Exon 6 of 6		XP_016857636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZFP69B	ENST00000361584.5 link	c.445A>G	p.Ser149Gly	missense_variant	Exon 5 of 5	1	NM_023070.3	ENSP00000354547.4	Q9UJL9-1
ZFP69B	ENST00000484445.5 link	c.359A>G	p.Glu120Gly	missense_variant	Exon 5 of 5	1		ENSP00000435907.1	E9PS66
ZFP69B	ENST00000411995.6 link	c.445A>G	p.Ser149Gly	missense_variant	Exon 6 of 6	5		ENSP00000399664.2	Q9UJL9-1
ZFP69B	ENST00000469416.1 link	n.1097A>G		non_coding_transcript_exon_variant	Exon 5 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000684

AC:

AN:

219166

Hom.:

AF XY:

0.000101

AC XY:

AN XY:

119326

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:

0.00

Gnomad FIN exome

AF:

0.000146

Gnomad NFE exome

AF:

0.000116

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000504

AC:

AN:

1428326

Hom.:

Cov.:

AF XY:

0.0000592

AC XY:

AN XY:

709294

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:

0.000171

Gnomad4 NFE exome

AF:

0.0000572

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000616

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.445A>G (p.S149G) alteration is located in exon 5 (coding exon 5) of the ZFP69B gene. This alteration results from a A to G substitution at nucleotide position 445, causing the serine (S) at amino acid position 149 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

0.071

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.3

DANN

Benign

0.91

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.000030

LIST_S2

Benign

0.34

M_CAP

Benign

0.0017

MetaRNN

Benign

0.064

MetaSVM

Benign

-0.99

PROVEAN

Benign

-1.5

REVEL

Benign

0.027

Sift

Pathogenic

0.0

Vest4

0.15

MutPred

0.28

Gain of loop (P = 0.0079);

MVP

0.18

ClinPred

0.050

GERP RS

0.97

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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