Genetic Variant ZNF680:p.His424Arg (chr7-64521483-T-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_178558.5(ZNF680):c.1271A>G(p.His424Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. H424P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNF680
NM_178558.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.72

Publications

0 publications found

Variant links:

Genes affected

ZNF680 (HGNC:26897): (zinc finger protein 680) 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF680 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.765

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178558.5. 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
	ZNF680	NM_178558.5	MANE Select	c.1271A>G	p.His424Arg	missense	Exon 4 of 4	NP_848653.2	Q8NEM1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF680	ENST00000309683.11	TSL:1 MANE Select	c.1271A>G	p.His424Arg	missense	Exon 4 of 4	ENSP00000309330.6	Q8NEM1-1
ZNF680	ENST00000920524.1		c.1313A>G	p.His438Arg	missense	Exon 4 of 4	ENSP00000590583.1
ZNF680	ENST00000920523.1		c.1175A>G	p.His392Arg	missense	Exon 3 of 3	ENSP00000590582.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461432

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727026

African (AFR)

AF:

0.00

AC:

AN:

33450

American (AMR)

AF:

0.00

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.00

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53272

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111832

Other (OTH)

AF:

0.00

AC:

AN:

60374

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

Pathogenic

0.88

BayesDel_addAF

Uncertain

0.097

BayesDel_noAF

Benign

-0.10

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.49

Eigen

Uncertain

0.25

Eigen_PC

Benign

-0.072

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.42

M_CAP

Benign

0.0034

MetaRNN

Pathogenic

0.76

MetaSVM

Uncertain

0.50

MutationAssessor

Pathogenic

4.2

PhyloP100

5.7

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-7.7

REVEL

Uncertain

0.35

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.26

MutPred

0.79

Gain of MoRF binding (P = 0.0438)

MVP

0.91

MPC

0.18

ClinPred

0.99

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.41

gMVP

0.17

Mutation Taster

=94/6

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

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