7-64521345-A-C

Variant names:

• chr7-64521345-A-C
• NM_178558.5:c.1409T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178558.5(ZNF680):​c.1409T>G​(p.Val470Gly) 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. 15/21 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: -2.42

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10124788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF680	NM_178558.5	c.1409T>G	p.Val470Gly	missense_variant	Exon 4 of 4	ENST00000309683.11	NP_848653.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF680	ENST00000309683.11	c.1409T>G	p.Val470Gly	missense_variant	Exon 4 of 4	1	NM_178558.5	ENSP00000309330.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1409T>G (p.V470G) alteration is located in exon 4 (coding exon 4) of the ZNF680 gene. This alteration results from a T to G substitution at nucleotide position 1409, causing the valine (V) at amino acid position 470 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.3
DANN	Benign	0.84
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0051	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.55	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.033
Sift	Benign	0.044	D
Sift4G	Uncertain	0.031	D
Polyphen		0.20	B
Vest4		0.095
MutPred		0.71		Loss of stability (P = 0.024);
MVP		0.099
MPC		0.023
ClinPred		0.11	T
GERP RS		0.16
Varity_R		0.066
gMVP		0.035

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-63981723;