1-200407092-T-A

Position:

• chr1-200407092-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001281293.2(ZNF281):​c.2614A>T​(p.Thr872Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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: ZNF281 NM_001281293.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.80

Genes affected

ZNF281 (HGNC:13075): (zinc finger protein 281) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of gene expression; negative regulation of transcription by RNA polymerase II; and positive regulation of transcription, DNA-templated. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000230623 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.101994365).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF281	NM_001281293.2	c.2614A>T	p.Thr872Ser	missense_variant	2/2	ENST00000367353.2	NP_001268222.1
ZNF281	NM_012482.5	c.2614A>T	p.Thr872Ser	missense_variant	2/2		NP_036614.1
ZNF281	NM_001281294.2	c.2506A>T	p.Thr836Ser	missense_variant	3/3		NP_001268223.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF281	ENST00000367353.2	c.2614A>T	p.Thr872Ser	missense_variant	2/2	1	NM_001281293.2	ENSP00000356322.1
ZNF281	ENST00000294740.3	c.2614A>T	p.Thr872Ser	missense_variant	2/2	1		ENSP00000294740.2
ZNF281	ENST00000367352.3	c.2506A>T	p.Thr836Ser	missense_variant	3/3	2		ENSP00000356321.3
ENSG00000230623	ENST00000637430.1	n.484+43564T>A		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Mar 30, 2024

The c.2614A>T (p.T872S) alteration is located in exon 2 (coding exon 1) of the ZNF281 gene. This alteration results from a A to T substitution at nucleotide position 2614, causing the threonine (T) at amino acid position 872 to be replaced by a serine (S). 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	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.18	T;T;.
Eigen	Benign	-0.093
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.70	.;T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.63	N;N;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.50	N;N;N
REVEL	Benign	0.070
Sift	Benign	0.25	T;T;T
Sift4G	Benign	0.36	T;T;T
Polyphen		0.036	B;B;.
Vest4		0.16
MVP		0.068
MPC		0.52
ClinPred		0.49	T
GERP RS		5.7
Varity_R		0.13
gMVP		0.37

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: chr1-200376220;