19-57290767-C-T

Position:

• chr19-57290767-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000360338.4(ZNF460):​c.226C>T​(p.Leu76Phe) 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: 32)
• Consequence: ZNF460 ENST00000360338.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.13

Genes affected

ZNF460 (HGNC:21628): (zinc finger protein 460) Zinc finger proteins, such as ZNF272, interact with nucleic acids and have diverse functions. The zinc finger domain is a conserved amino acid sequence motif containing 2 specifically positioned cysteines and 2 histidines that are involved in coordinating zinc. Kruppel-related proteins form 1 family of zinc finger proteins. See ZFP93 (MIM 604749) for additional information on zinc finger proteins.[supplied by OMIM, May 2004]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048312753).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF460	NM_006635.4	c.226C>T	p.Leu76Phe	missense_variant	3/3	ENST00000360338.4	NP_006626.3
ZNF460	NM_001330622.2	c.103C>T	p.Leu35Phe	missense_variant	3/3		NP_001317551.1
ZNF460	XM_047438079.1	c.205C>T	p.Leu69Phe	missense_variant	3/3		XP_047294035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF460	ENST00000360338.4	c.226C>T	p.Leu76Phe	missense_variant	3/3	1	NM_006635.4	ENSP00000353491.2
ZNF460	ENST00000537645.5	c.103C>T	p.Leu35Phe	missense_variant	3/3	2		ENSP00000446167.1
ZNF460	ENST00000599602.1	c.103C>T	p.Leu35Phe	missense_variant	3/3	4		ENSP00000471285.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Aug 20, 2023

The c.226C>T (p.L76F) alteration is located in exon 3 (coding exon 3) of the ZNF460 gene. This alteration results from a C to T substitution at nucleotide position 226, causing the leucine (L) at amino acid position 76 to be replaced by a phenylalanine (F). 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	0.081
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	.;T;.
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.16	T;T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.048	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	.;L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.42	N;N;.
REVEL	Benign	0.062
Sift	Benign	0.56	T;T;.
Sift4G	Benign	0.54	T;T;T
Polyphen		0.94	.;P;.
Vest4		0.054
MutPred		0.19		.;Loss of disorder (P = 0.1306);.;
MVP		0.10
MPC		0.70
ClinPred		0.12	T
GERP RS		1.1
Varity_R		0.074
gMVP		0.024

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: chr19-57802135;