19-57941457-T-G

Variant names:

• chr19-57941457-T-G
• NM_005773.3:c.1351A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005773.3(ZNF256):​c.1351A>C​(p.Ile451Leu) 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. 16/22 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: ZNF256 NM_005773.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.46
• Publications: 0 publications found

Genes affected

ZNF256 (HGNC:13049): (zinc finger protein 256) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription, DNA-templated. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053402454).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005773.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF256	NM_005773.3	MANE Select	c.1351A>C	p.Ile451Leu	missense	Exon 3 of 3	NP_005764.2
	ZNF256	NM_001375403.1		c.892A>C	p.Ile298Leu	missense	Exon 2 of 2	NP_001362332.1	Q9Y2P7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF256	ENST00000282308.4	TSL:1 MANE Select	c.1351A>C	p.Ile451Leu	missense	Exon 3 of 3	ENSP00000282308.2	Q9Y2P7-1
	ZNF256	ENST00000598928.1	TSL:1	c.*1053A>C		3_prime_UTR	Exon 2 of 2	ENSP00000472858.1	M0R2X0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.92
DANN	Benign	0.84
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.21	N
PhyloP100		-1.5
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.010
Sift	Benign	0.21	T
Sift4G	Benign	0.34	T
Polyphen		0.0080	B
Vest4		0.073
MutPred		0.37		Gain of disorder (P = 0.0513)
MVP		0.12
MPC		0.058
ClinPred		0.060	T
GERP RS		-5.3
Varity_R		0.040
gMVP		0.024
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

hg19: chr19-58452825;