19-36514229-C-T

Position:

• chr19-36514229-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001166037.2(ZNF260):​c.1010G>A​(p.Cys337Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF260 NM_001166037.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.67

Genes affected

ZNF260 (HGNC:13499): (zinc finger protein 260) 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 by RNA polymerase II. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.844

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF260	NM_001166037.2	c.1010G>A	p.Cys337Tyr	missense_variant	3/3	ENST00000523638.6	NP_001159509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF260	ENST00000523638.6	c.1010G>A	p.Cys337Tyr	missense_variant	3/3	2	NM_001166037.2	ENSP00000429803.1
ZNF260	ENST00000588993.1	c.1010G>A	p.Cys337Tyr	missense_variant	3/3	1		ENSP00000467219.1
ZNF260	ENST00000592282.1	c.1010G>A	p.Cys337Tyr	missense_variant	4/4	1		ENSP00000464964.1
ZNF260	ENST00000593142.5	c.1010G>A	p.Cys337Tyr	missense_variant	2/2	1		ENSP00000465834.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461820 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727212

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

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

Mar 24, 2023

The c.1010G>A (p.C337Y) alteration is located in exon 4 (coding exon 1) of the ZNF260 gene. This alteration results from a G to A substitution at nucleotide position 1010, causing the cysteine (C) at amino acid position 337 to be replaced by a tyrosine (Y). 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	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T;T;T;T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.55	.;.;.;T
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.84	D;D;D;D
MetaSVM	Pathogenic	0.92	D
MutationAssessor	Pathogenic	3.9	H;H;H;H
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-11	D;.;.;.
REVEL	Pathogenic	0.72
Sift	Uncertain	0.0080	D;.;.;.
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.53
MutPred		0.77		Loss of ubiquitination at K339 (P = 0.0787);Loss of ubiquitination at K339 (P = 0.0787);Loss of ubiquitination at K339 (P = 0.0787);Loss of ubiquitination at K339 (P = 0.0787);
MVP		0.90
MPC		0.68
ClinPred		1.0	D
GERP RS		4.3
Varity_R		0.76
gMVP		0.23

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: chr19-37005131;