chr19-52613764-T-G

Variant names:

• chr19-52613764-T-G
• rs7248435
• NM_018300.4:c.801A>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_018300.4(ZNF83):​c.801A>C​(p.Gly267Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000021 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000034 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF83 NM_018300.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• Publications: 12 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=-2.36 with no splicing effect.

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.801A>C	p.Gly267Gly	synonymous	Exon 3 of 3	NP_060770.3
	ZNF83	NM_001105549.2		c.801A>C	p.Gly267Gly	synonymous	Exon 6 of 6	NP_001099019.1	P51522-1
	ZNF83	NM_001105550.2		c.801A>C	p.Gly267Gly	synonymous	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.801A>C	p.Gly267Gly	synonymous	Exon 3 of 3	ENSP00000301096.3	P51522-1
	ZNF83	ENST00000597597.1	TSL:1	c.801A>C	p.Gly267Gly	synonymous	Exon 2 of 2	ENSP00000472619.1	P51522-1
	ZNF83	ENST00000541777.6	TSL:1	n.2357A>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0000206 AC: 2 AN: 97272 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000436

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000444 AC: 8 AN: 180344 AF XY: 0.0000404

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000126

Gnomad NFE exome AF: 0.0000691

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000340 AC: 33 AN: 969912 Hom.: 1 Cov.: 31 AF XY: 0.0000370 AC XY: 18 AN XY: 486964

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000419 AC: 1 AN: 23870

American (AMR) AF: 0.00 AC: 0 AN: 11330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20302

East Asian (EAS) AF: 0.0000905 AC: 1 AN: 11048

South Asian (SAS) AF: 0.0000151 AC: 1 AN: 66278

European-Finnish (FIN) AF: 0.000182 AC: 6 AN: 32912

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4612

European-Non Finnish (NFE) AF: 0.0000303 AC: 23 AN: 759948

Other (OTH) AF: 0.0000252 AC: 1 AN: 39612

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000205 AC: 2 AN: 97350 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 46870

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29156

American (AMR) AF: 0.00 AC: 0 AN: 6070

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2678

East Asian (EAS) AF: 0.00 AC: 0 AN: 1340

South Asian (SAS) AF: 0.00 AC: 0 AN: 3560

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 226

European-Non Finnish (NFE) AF: 0.0000436 AC: 2 AN: 45838

Other (OTH) AF: 0.00 AC: 0 AN: 1402

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.174 Hom.: 248

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.20
DANN	Benign	0.37
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs7248435; hg19: chr19-53117017; COSMIC: COSV56528530; COSMIC: COSV56528530;