19-19880104-C-T

Variant names:

• chr19-19880104-C-T
• rs761847160
• NM_021047.3:c.184C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021047.3(ZNF253):​c.184C>T​(p.Pro62Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P62T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZNF253 NM_021047.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.984
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11576325).

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.184C>T	p.Pro62Ser	missense	Exon 3 of 4	NP_066385.2	O75346-1
	ZNF253	NM_001331133.1		c.-9C>T		5_prime_UTR	Exon 2 of 3	NP_001318062.1	O75346
	ZNF253	NM_001331134.1		c.-2-11370C>T		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.184C>T	p.Pro62Ser	missense	Exon 3 of 4	ENSP00000468720.1	O75346-1
	ZNF253	ENST00000355650.4	TSL:1	c.-2-11370C>T		intron	N/A	ENSP00000347868.4	O75346-2
	ZNF253	ENST00000937512.1		c.184C>T	p.Pro62Ser	missense	Exon 3 of 4	ENSP00000607571.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457006 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724836

African (AFR) AF: 0.00 AC: 0 AN: 33270

American (AMR) AF: 0.00 AC: 0 AN: 44224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25994

East Asian (EAS) AF: 0.00 AC: 0 AN: 39470

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109822

Other (OTH) AF: 0.00 AC: 0 AN: 60090

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	11
DANN	Benign	0.85
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0080	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.98
PrimateAI	Benign	0.44	T
Sift4G	Benign	0.080	T
Polyphen		0.21	B
Vest4		0.14
MutPred		0.57		Loss of methylation at K61 (P = 0.0647)
MVP		0.23
MPC		0.12
ClinPred		0.077	T
GERP RS		0.44
Varity_R		0.090
gMVP		0.044
Mutation Taster		=98/2	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: rs761847160; hg19: chr19-19990913;