3-114236492-C-A

Position:

• chr3-114236492-C-A

Variant summary

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

The NM_007136.4(ZNF80):​c.583G>T​(p.Gly195Trp) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF80 NM_007136.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.611

Genes affected

ZNF80 (HGNC:13155): (zinc finger protein 80) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm. [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=0.34444785).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF80	NM_007136.4	c.583G>T	p.Gly195Trp	missense_variant	1/1	ENST00000482457.4	NP_009067.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF80	ENST00000482457.4	c.583G>T	p.Gly195Trp	missense_variant	1/1		NM_007136.4	ENSP00000417192	P1
ZNF80	ENST00000308095.4	c.583G>T	p.Gly195Trp	missense_variant, NMD_transcript_variant	1/2	1		ENSP00000309812

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 14, 2023

The c.583G>T (p.G195W) alteration is located in exon 1 (coding exon 1) of the ZNF80 gene. This alteration results from a G to T substitution at nucleotide position 583, causing the glycine (G) at amino acid position 195 to be replaced by a tryptophan (W). 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	Uncertain	0.45
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T;T
Eigen	Benign	-0.062
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.36	.;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.9	H;H
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-7.6	D;.
REVEL	Benign	0.059
Sift	Benign	0.068	T;.
Sift4G	Uncertain	0.010	D;D
Polyphen		1.0	D;D
Vest4		0.31
MutPred		0.59		Loss of disorder (P = 0.0043);Loss of disorder (P = 0.0043);
MVP		0.081
MPC		0.57
ClinPred		0.93	D
GERP RS		1.2
Varity_R		0.11
gMVP		0.019

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: chr3-113955339; COSMIC: COSV57362563; COSMIC: COSV57362563;