19-36514967-G-T

Position:

• chr19-36514967-G-T

Variant summary

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

The NM_001166037.2(ZNF260):​c.272C>A​(p.Ala91Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZNF260 NM_001166037.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.310

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19170123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF260	NM_001166037.2	c.272C>A	p.Ala91Asp	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.272C>A	p.Ala91Asp	missense_variant	3/3	2	NM_001166037.2	ENSP00000429803.1
ZNF260	ENST00000588993.1	c.272C>A	p.Ala91Asp	missense_variant	3/3	1		ENSP00000467219.1
ZNF260	ENST00000592282.1	c.272C>A	p.Ala91Asp	missense_variant	4/4	1		ENSP00000464964.1
ZNF260	ENST00000593142.5	c.272C>A	p.Ala91Asp	missense_variant	2/2	1		ENSP00000465834.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461752 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727174

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: 0.00000270

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 31, 2024

The c.272C>A (p.A91D) alteration is located in exon 4 (coding exon 1) of the ZNF260 gene. This alteration results from a C to A substitution at nucleotide position 272, causing the alanine (A) at amino acid position 91 to be replaced by an aspartic acid (D). 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	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	T;T;T;T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.18	.;.;.;T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.3	L;L;L;L
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.9	D;.;.;.
REVEL	Benign	0.071
Sift	Uncertain	0.014	D;.;.;.
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		0.45	P;P;P;P
Vest4		0.37
MutPred		0.53		Gain of ubiquitination at K95 (P = 0.0339);Gain of ubiquitination at K95 (P = 0.0339);Gain of ubiquitination at K95 (P = 0.0339);Gain of ubiquitination at K95 (P = 0.0339);
MVP		0.41
MPC		0.23
ClinPred		0.22	T
GERP RS		-2.0
Varity_R		0.36
gMVP		0.042

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: chr19-37005869;