rs527593247

Variant names:

• chr19-57940938-C-T
• rs527593247
• NM_005773.3:c.1870G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-57940938-C-T
• chr19-57940938-C-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005773.3(ZNF256):​c.1870G>A​(p.Val624Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,613,302 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: ZNF256 NM_005773.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.449
• Publications: 4 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.049611986).

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.1870G>A	p.Val624Ile	missense	Exon 3 of 3	NP_005764.2
	ZNF256	NM_001375403.1		c.1411G>A	p.Val471Ile	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.1870G>A	p.Val624Ile	missense	Exon 3 of 3	ENSP00000282308.2	Q9Y2P7-1
	ZNF256	ENST00000598928.1	TSL:1	c.*1572G>A		3_prime_UTR	Exon 2 of 2	ENSP00000472858.1	M0R2X0

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152156 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000558 AC: 14 AN: 251006 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000274 AC: 40 AN: 1461146 Hom.: 0 Cov.: 30 AF XY: 0.0000344 AC XY: 25 AN XY: 726774

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.0000671 AC: 3 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39682

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000900 AC: 10 AN: 1111430

Other (OTH) AF: 0.0000994 AC: 6 AN: 60378

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152156 Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3 AN XY: 74330

African (AFR) AF: 0.0000241 AC: 1 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000412 AC: 5

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.073
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.73
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.14	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.63	N
PhyloP100		0.45
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.065
Sift	Benign	0.43	T
Sift4G	Benign	0.31	T
Polyphen		0.052	B
Vest4		0.067
MutPred		0.47		Gain of methylation at K626 (P = 0.0774)
MVP		0.061
MPC		0.049
ClinPred		0.014	T
GERP RS		-1.8
Varity_R		0.0096
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

dbSNP: rs527593247; hg19: chr19-58452306; COSMIC: COSV56596685;