rs771336818

Variant names:

• chr7-64521939-C-A
• NM_178558.5:c.815G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-64521939-C-A
• chr7-64521939-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_178558.5(ZNF680):​c.815G>T​(p.Gly272Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. G272D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF680 NM_178558.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42109245).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF680	NM_178558.5	c.815G>T	p.Gly272Val	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.815G>T	p.Gly272Val	missense_variant	Exon 4 of 4	1	NM_178558.5	ENSP00000309330.6
ZNF680	ENST00000476563.1	n.756G>T		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460772 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726680

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.16
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.027	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Pathogenic	3.2	M
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-8.5	D
REVEL	Benign	0.22
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.25
MutPred		0.61		Loss of disorder (P = 0.0345);
MVP		0.56
MPC		0.18
ClinPred		0.99	D
GERP RS		1.2
Varity_R		0.37
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: chr7-63982317;