chr19-36514862-T-A

Position:

• chr19-36514862-T-A

Variant summary

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

The NM_001166037.2(ZNF260):​c.377A>T​(p.His126Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 2.86

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF260	NM_001166037.2	c.377A>T	p.His126Leu	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.377A>T	p.His126Leu	missense_variant	3/3	2	NM_001166037.2	ENSP00000429803	P1
ZNF260	ENST00000588993.1	c.377A>T	p.His126Leu	missense_variant	3/3	1		ENSP00000467219	P1
ZNF260	ENST00000592282.1	c.377A>T	p.His126Leu	missense_variant	4/4	1		ENSP00000464964	P1
ZNF260	ENST00000593142.5	c.377A>T	p.His126Leu	missense_variant	2/2	1		ENSP00000465834	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

Jul 05, 2023

The c.377A>T (p.H126L) alteration is located in exon 4 (coding exon 1) of the ZNF260 gene. This alteration results from a A to T substitution at nucleotide position 377, causing the histidine (H) at amino acid position 126 to be replaced by a leucine (L). 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	0.16
BayesDel_addAF	Uncertain	0.099	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	18
DANN	Benign	0.90
DEOGEN2	Benign	0.28	T;T;T;T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.061
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.70	.;.;.;T
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.62	D;D;D;D
MetaSVM	Uncertain	0.38	D
MutationAssessor	Pathogenic	4.0	H;H;H;H
MutationTaster	Benign	0.94	N;N;N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-8.0	D;.;.;.
REVEL	Uncertain	0.42
Sift	Pathogenic	0.0	D;.;.;.
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.53	P;P;P;P
Vest4		0.36
MutPred		0.67		Loss of disorder (P = 0.0404);Loss of disorder (P = 0.0404);Loss of disorder (P = 0.0404);Loss of disorder (P = 0.0404);
MVP		0.87
MPC		0.13
ClinPred		0.73	D
GERP RS		4.3
Varity_R		0.58
gMVP		0.18

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: chr19-37005764;