NM_021047.3:c.68C>G

Variant names:

• chr19-19878545-C-G
• NM_021047.3:c.68C>G

Variant summary

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

The NM_021047.3(ZNF253):​c.68C>G​(p.Thr23Ser) 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. 14/20 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF253 NM_021047.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0940
• Publications: 0 publications found

Genes affected

ZNF253 (HGNC:13497): (zinc finger protein 253) 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, DNA-templated. Predicted to be located in nucleus. [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=0.06266704).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021047.3. 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
	ZNF253	NM_021047.3	MANE Select	c.68C>G	p.Thr23Ser	missense	Exon 2 of 4	NP_066385.2	O75346-1
	ZNF253	NM_001331133.1		c.-62-1506C>G		intron	N/A	NP_001318062.1	O75346
	ZNF253	NM_001331134.1		c.-3+12546C>G		intron	N/A	NP_001318063.1	O75346-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF253	ENST00000589717.2	TSL:1 MANE Select	c.68C>G	p.Thr23Ser	missense	Exon 2 of 4	ENSP00000468720.1	O75346-1
	ZNF253	ENST00000355650.4	TSL:1	c.-3+12546C>G		intron	N/A	ENSP00000347868.4	O75346-2
	ZNF253	ENST00000937512.1		c.68C>G	p.Thr23Ser	missense	Exon 2 of 4	ENSP00000607571.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461756 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727174

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111948

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

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	0.12
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.28
DEOGEN2	Benign	0.14	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.015	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.67	N
PhyloP100		0.094
PrimateAI	Benign	0.43	T
Sift4G	Benign	0.38	T
Polyphen		0.89	P
Vest4		0.067
MutPred		0.41		Loss of phosphorylation at T23 (P = 0.152)
MVP		0.21
MPC		0.16
ClinPred		0.14	T
GERP RS		-1.9
Varity_R		0.060
gMVP		0.037
Mutation Taster		=95/5	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: chr19-19989354;