chr19-36514187-A-T

Position:

• chr19-36514187-A-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.1052T>A​(p.Met351Lys) 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. 14/21 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: ZNF260 NM_001166037.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.70

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=0.16678336).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF260	NM_001166037.2	c.1052T>A	p.Met351Lys	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.1052T>A	p.Met351Lys	missense_variant	3/3	2	NM_001166037.2	ENSP00000429803	P1
ZNF260	ENST00000588993.1	c.1052T>A	p.Met351Lys	missense_variant	3/3	1		ENSP00000467219	P1
ZNF260	ENST00000592282.1	c.1052T>A	p.Met351Lys	missense_variant	4/4	1		ENSP00000464964	P1
ZNF260	ENST00000593142.5	c.1052T>A	p.Met351Lys	missense_variant	2/2	1		ENSP00000465834	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

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

Jan 04, 2024

The c.1052T>A (p.M351K) alteration is located in exon 4 (coding exon 1) of the ZNF260 gene. This alteration results from a T to A substitution at nucleotide position 1052, causing the methionine (M) at amino acid position 351 to be replaced by a lysine (K). 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	0.30
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Benign	0.91
DEOGEN2	Benign	0.015	T;T;T;T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.23	.;.;.;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;L;L;L
MutationTaster	Benign	0.74	D;D;D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.35	N;.;.;.
REVEL	Benign	0.11
Sift	Benign	0.061	T;.;.;.
Sift4G	Uncertain	0.035	D;D;D;D
Polyphen		0.026	B;B;B;B
Vest4		0.46
MutPred		0.59		Gain of methylation at M351 (P = 0.013);Gain of methylation at M351 (P = 0.013);Gain of methylation at M351 (P = 0.013);Gain of methylation at M351 (P = 0.013);
MVP		0.59
MPC		0.20
ClinPred		0.22	T
GERP RS		2.0
Varity_R		0.28
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr19-37005089;