chr7-64521367-T-C

Variant names:

• chr7-64521367-T-C
• NM_178558.5:c.1387A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178558.5(ZNF680):​c.1387A>G​(p.Lys463Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF680 NM_178558.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.26
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15766823).

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.1387A>G	p.Lys463Glu	missense	Exon 4 of 4	NP_848653.2	Q8NEM1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF680	ENST00000309683.11	TSL:1 MANE Select	c.1387A>G	p.Lys463Glu	missense	Exon 4 of 4	ENSP00000309330.6	Q8NEM1-1
	ZNF680	ENST00000920524.1		c.1429A>G	p.Lys477Glu	missense	Exon 4 of 4	ENSP00000590583.1
	ZNF680	ENST00000920523.1		c.1291A>G	p.Lys431Glu	missense	Exon 3 of 3	ENSP00000590582.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	19
DANN	Benign	0.91
DEOGEN2	Benign	0.077	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.0062	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		-2.3
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.030
Sift	Uncertain	0.016	D
Sift4G	Benign	0.27	T
Polyphen		1.0	D
Vest4		0.078
MutPred		0.32		Loss of methylation at K463 (P = 2e-04)
MVP		0.21
MPC		0.10
ClinPred		0.44	T
GERP RS		-2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.20
gMVP		0.017
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

hg19: chr7-63981745;