rs2195980

Positions:

• chr19-43847542-C-A
• chr19-43847542-C-T

Variant summary

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

The NM_181845.2(ZNF283):​c.941C>A​(p.Thr314Asn) 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. 13/21 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. T314I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 29)
• Consequence: ZNF283 NM_181845.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.552

Genes affected

ZNF283 (HGNC:13077): (zinc finger protein 283) 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 by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.09462112).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF283	NM_181845.2	c.941C>A	p.Thr314Asn	missense_variant	7/7	ENST00000618787.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF283	ENST00000618787.5	c.941C>A	p.Thr314Asn	missense_variant	7/7	2	NM_181845.2	A2
ZNF283	ENST00000324461.9	c.941C>A	p.Thr314Asn	missense_variant	4/4	1		A2
ZNF283	ENST00000650832.1	c.833C>A	p.Thr278Asn	missense_variant	7/7			P2
ZNF283	ENST00000588797.6	c.*541C>A		3_prime_UTR_variant	6/6	2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 75

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.035	T;T;T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.039	.;T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.095	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.;L
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.2	.;.;D
REVEL	Benign	0.029
Sift	Uncertain	0.0030	.;.;D
Sift4G	Uncertain	0.027	D;D;D
Polyphen		0.0010	B;.;B
Vest4		0.18
MutPred		0.36		Gain of MoRF binding (P = 0.1155);.;Gain of MoRF binding (P = 0.1155);
MVP		0.24
MPC		0.35
ClinPred		0.58	D
GERP RS		2.0
Varity_R		0.28
gMVP		0.021

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

LitVar

Other links and lift over

dbSNP: rs2195980; hg19: chr19-44351694;