chr19-52613471-A-G

Variant names:

• chr19-52613471-A-G
• rs1294064240
• ENST00000301096.8:c.1094T>C

Variant summary

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

The ENST00000301096.8(ZNF83):​c.1094T>C​(p.Ile365Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. I365K) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: ZNF83 ENST00000301096.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07766992).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF83	NM_001105549.2	c.1094T>C	p.Ile365Thr	missense_variant	Exon 6 of 6		NP_001099019.1
ZNF83	NM_001105550.2	c.1094T>C	p.Ile365Thr	missense_variant	Exon 5 of 5		NP_001099020.1
ZNF83	NM_001105551.2	c.1094T>C	p.Ile365Thr	missense_variant	Exon 5 of 5		NP_001099021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF83	ENST00000301096.8	c.1094T>C	p.Ile365Thr	missense_variant	Exon 3 of 3	3		ENSP00000301096.3

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151744 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151744 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74118

African (AFR) AF: 0.00 AC: 0 AN: 41268

American (AMR) AF: 0.0000656 AC: 1 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5122

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67946

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.023
DANN	Benign	0.58
DEOGEN2	Benign	0.0026	T;T;T;T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.096	.;T;.;.;.
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.078	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.41	N;N;N;N;N
PhyloP100		-1.8
PROVEAN	Benign	0.56	N;N;.;N;N
REVEL	Benign	0.015
Sift	Benign	0.10	T;T;.;T;T
Sift4G	Benign	0.082	T;T;T;T;T
Polyphen		0.22	B;B;B;B;B
Vest4		0.041
MutPred		0.54		Loss of stability (P = 0.0126);Loss of stability (P = 0.0126);Loss of stability (P = 0.0126);Loss of stability (P = 0.0126);Loss of stability (P = 0.0126);
MVP		0.23
MPC		0.12
ClinPred		0.083	T
GERP RS		-4.3
Varity_R		0.026
gMVP		0.0084
Mutation Taster		=100/0	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: rs1294064240; hg19: chr19-53116724;