dbSNP rs769989618: ZFP69:p.Pro68Gln (chr1-40481838-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001320179.2(ZFP69):c.203C>A(p.Pro68Gln) 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 1,460,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P68L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZFP69
NM_001320179.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.69

Publications

0 publications found

Variant links:

Genes affected

ZFP69 (HGNC:24708): (ZFP69 zinc finger protein) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II and regulation of lipid metabolic process. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZFP69 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.056581795).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320179.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFP69	NM_001320179.2	MANE Select	c.203C>A	p.Pro68Gln	missense	Exon 3 of 6	NP_001307108.1	Q49AA0
ZFP69	NM_001320178.2		c.203C>A	p.Pro68Gln	missense	Exon 3 of 6	NP_001307107.1
ZFP69	NM_198494.3		c.203C>A	p.Pro68Gln	missense	Exon 3 of 6	NP_940896.2	Q49AA0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFP69	ENST00000372706.6	TSL:1 MANE Select	c.203C>A	p.Pro68Gln	missense	Exon 3 of 6	ENSP00000361791.1	Q49AA0
ZFP69	ENST00000853135.1		c.203C>A	p.Pro68Gln	missense	Exon 3 of 6	ENSP00000523194.1
ZFP69	ENST00000853137.1		c.203C>A	p.Pro68Gln	missense	Exon 3 of 6	ENSP00000523196.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460010

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726464

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33440

American (AMR)

AF:

0.00

AC:

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26078

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86082

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53328

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110674

Other (OTH)

AF:

0.00

AC:

AN:

60300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.047

(source)

DANN

Benign

0.50

DEOGEN2

Benign

0.020

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.036

M_CAP

Benign

0.0018

MetaRNN

Benign

0.057

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.1

PhyloP100

-1.7

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.70

REVEL

Benign

0.012

Sift

Benign

0.36

Sift4G

Benign

0.090

Polyphen

0.0040

Vest4

0.16

MutPred

0.18

Loss of glycosylation at T69 (P = 0.0466)

MVP

0.061

MPC

0.16

ClinPred

0.046

GERP RS

-7.1

Varity_R

0.025

gMVP

0.15

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over