chr19-52613457-C-T

Variant names:

• chr19-52613457-C-T
• rs1568522955
• NM_018300.4:c.1108G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018300.4(ZNF83):​c.1108G>A​(p.Glu370Lys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF83 NM_018300.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.23
• Publications: 0 publications found

Genes affected

ZNF83 (HGNC:13158): (zinc finger protein 83) 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 located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000269825 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2677399).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018300.4. 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
	ZNF83	NM_018300.4	MANE Select	c.1108G>A	p.Glu370Lys	missense	Exon 3 of 3	NP_060770.3
	ZNF83	NM_001105549.2		c.1108G>A	p.Glu370Lys	missense	Exon 6 of 6	NP_001099019.1	P51522-1
	ZNF83	NM_001105550.2		c.1108G>A	p.Glu370Lys	missense	Exon 5 of 5	NP_001099020.1	P51522-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF83	ENST00000301096.8	TSL:3 MANE Select	c.1108G>A	p.Glu370Lys	missense	Exon 3 of 3	ENSP00000301096.3	P51522-1
	ZNF83	ENST00000597597.1	TSL:1	c.1108G>A	p.Glu370Lys	missense	Exon 2 of 2	ENSP00000472619.1	P51522-1
	ZNF83	ENST00000541777.6	TSL:1	n.2664G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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	0.17
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.2
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.11
Sift	Uncertain	0.0050	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.23
MutPred		0.54		Gain of methylation at E370 (P = 0.0056)
MVP		0.45
MPC		0.40
ClinPred		0.89	D
GERP RS		1.1
Varity_R		0.30
gMVP		0.020
Mutation Taster		=99/1	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: rs1568522955; hg19: chr19-53116710; COSMIC: COSV99991630; COSMIC: COSV99991630;