ENST00000301096.8:c.922T>G

Variant names:

• chr19-52613643-A-C
• ENST00000301096.8:c.922T>G

Variant summary

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

The ENST00000301096.8(ZNF83):​c.922T>G​(p.Trp308Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. W308R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF83 ENST00000301096.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110

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]

ENSG00000290073 (HGNC:):

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=0.05987826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF83	NM_001105549.2	c.922T>G	p.Trp308Gly	missense_variant	Exon 6 of 6		NP_001099019.1
ZNF83	NM_001105550.2	c.922T>G	p.Trp308Gly	missense_variant	Exon 5 of 5		NP_001099020.1
ZNF83	NM_001105551.2	c.922T>G	p.Trp308Gly	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.922T>G	p.Trp308Gly	missense_variant	Exon 3 of 3	3		ENSP00000301096.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461596 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727084

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	2.6
DANN	Benign	0.45
DEOGEN2	Benign	0.0019	T;T;T;T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.52	.;T;.;.;.
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.060	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.28	N;N;N;N;N
PROVEAN	Benign	-0.68	N;N;.;N;N
REVEL	Benign	0.031
Sift	Uncertain	0.0060	D;D;.;D;D
Sift4G	Uncertain	0.010	D;D;D;D;D
Polyphen		0.028	B;B;B;B;B
Vest4		0.12
MutPred		0.62		Gain of disorder (P = 0.0012);Gain of disorder (P = 0.0012);Gain of disorder (P = 0.0012);Gain of disorder (P = 0.0012);Gain of disorder (P = 0.0012);
MVP		0.10
MPC		0.11
ClinPred		0.081	T
GERP RS		-3.2
Varity_R		0.079
gMVP		0.090

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: chr19-53116896;