dbSNP rs545242034: ZNF684:p.Pro89Thr (chr1-40546588-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_152373.4(ZNF684):c.265C>A(p.Pro89Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. P89L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNF684
NM_152373.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.301

Publications

0 publications found

Variant links:

Genes affected

ZNF684 (HGNC:28418): (zinc finger protein 684) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to act upstream of or within innate immune response and negative regulation of single stranded viral RNA replication via double stranded DNA intermediate. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF684 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=0.030752063).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152373.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF684	NM_152373.4	MANE Select	c.265C>A	p.Pro89Thr	missense	Exon 5 of 5	NP_689586.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF684	ENST00000372699.8	TSL:1 MANE Select	c.265C>A	p.Pro89Thr	missense	Exon 5 of 5	ENSP00000361784.3	Q5T5D7
ZNF684	ENST00000921959.1		c.358C>A	p.Pro120Thr	missense	Exon 6 of 6	ENSP00000592018.1
ZNF684	ENST00000900102.1		c.313C>A	p.Pro105Thr	missense	Exon 5 of 5	ENSP00000570161.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1414750

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

700354

African (AFR)

AF:

0.00

AC:

AN:

31446

American (AMR)

AF:

0.00

AC:

AN:

35296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23596

East Asian (EAS)

AF:

0.00

AC:

AN:

39134

South Asian (SAS)

AF:

0.00

AC:

AN:

76852

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51992

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5540

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1092550

Other (OTH)

AF:

0.00

AC:

AN:

58344

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.53

DEOGEN2

Benign

0.0028

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.29

M_CAP

Benign

0.0030

MetaRNN

Benign

0.031

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.55

PhyloP100

-0.30

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.73

REVEL

Benign

0.049

Sift

Benign

0.58

Sift4G

Benign

0.64

Polyphen

0.0080

Vest4

0.079

MutPred

0.24

Gain of phosphorylation at P89 (P = 0.0174)

MVP

0.014

MPC

0.20

ClinPred

0.034

GERP RS

0.78

Varity_R

0.039

gMVP

0.092

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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