19-43847026-A-C

Position:

• chr19-43847026-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181845.2(ZNF283):​c.425A>C​(p.Asp142Ala) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF283 NM_181845.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.308

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061387718).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF283	NM_181845.2	c.425A>C	p.Asp142Ala	missense_variant	7/7	ENST00000618787.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF283	ENST00000618787.5	c.425A>C	p.Asp142Ala	missense_variant	7/7	2	NM_181845.2	A2
ZNF283	ENST00000324461.9	c.425A>C	p.Asp142Ala	missense_variant	4/4	1		A2
ZNF283	ENST00000650832.1	c.317A>C	p.Asp106Ala	missense_variant	7/7			P2
ZNF283	ENST00000588797.6	c.*25A>C		3_prime_UTR_variant	6/6	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 33

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

Sep 12, 2023

The c.425A>C (p.D142A) alteration is located in exon 7 (coding exon 4) of the ZNF283 gene. This alteration results from a A to C substitution at nucleotide position 425, causing the aspartic acid (D) at amino acid position 142 to be replaced by an alanine (A). 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	0.097
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.0093	T;T;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.22	.;T;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.061	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.095	N;.;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.8	.;.;N
REVEL	Benign	0.024
Sift	Benign	0.15	.;.;T
Sift4G	Benign	0.14	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.11
MutPred		0.28		Loss of ubiquitination at K145 (P = 0.0412);.;Loss of ubiquitination at K145 (P = 0.0412);
MVP		0.21
MPC		0.30
ClinPred		0.051	T
GERP RS		2.6
Varity_R		0.10
gMVP		0.055

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: chr19-44351178;