Genetic Variant NM_213603.3:c.670T>G (chr7-99486880-T-G) – 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_213603.3(ZNF789):c.670T>G(p.Phe224Val) 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. 15/22 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. F224L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ZNF789
NM_213603.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0940

Publications

0 publications found

Variant links:

Genes affected

ZNF789 (HGNC:27801): (zinc finger protein 789) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF789 links:

ZNF394 (HGNC:18832): (zinc finger protein 394) The protein encoded by this gene is a zinc finger protein that inhibits the transcription of mitogen-activated protein kinase signaling pathways. The encoded protein may be involved in cardiac function. [provided by RefSeq, Sep 2016]

ZNF394 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=0.053363144).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213603.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF789	NM_213603.3	MANE Select	c.670T>G	p.Phe224Val	missense	Exon 5 of 5	NP_998768.2	Q5FWF6-1
ZNF789	NM_001350999.2		c.619T>G	p.Phe207Val	missense	Exon 4 of 4	NP_001337928.1
ZNF789	NM_001351000.2		c.556T>G	p.Phe186Val	missense	Exon 4 of 4	NP_001337929.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF789	ENST00000331410.10	TSL:1 MANE Select	c.670T>G	p.Phe224Val	missense	Exon 5 of 5	ENSP00000331927.5	Q5FWF6-1
ZNF789	ENST00000481108.1	TSL:1	n.894T>G		non_coding_transcript_exon	Exon 2 of 2
ZNF789	ENST00000951821.1		c.682T>G	p.Phe228Val	missense	Exon 5 of 5	ENSP00000621880.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251466

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0033

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.73

M_CAP

Benign

0.0025

MetaRNN

Benign

0.053

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.26

PhyloP100

0.094

PrimateAI

Benign

0.32

PROVEAN

Benign

1.1

REVEL

Benign

0.023

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0020

Polyphen

0.017

Vest4

0.041

MutPred

0.64

Loss of catalytic residue at F224 (P = 0.0079)

MVP

0.24

MPC

0.24

ClinPred

0.20

GERP RS

1.5

Varity_R

0.087

gMVP

0.046

Mutation Taster

=93/7

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