19-52613741-T-G

Position:

• chr19-52613741-T-G

Variant summary

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

The NM_001277948.2(ZNF83):​c.824A>C​(p.His275Pro) 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. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 28)
• Consequence: ZNF83 NM_001277948.2 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -4.95

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]

(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=0.008855909).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF83	NM_018300.4	c.824A>C	p.His275Pro	missense_variant	3/3	ENST00000301096.8
ZNF83	NM_001277948.2	c.824A>C	p.His275Pro	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF83	ENST00000301096.8	c.824A>C	p.His275Pro	missense_variant	3/3	3	NM_018300.4	P1
	ENST00000702778.1	n.82-7358T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 28

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

literature only

James Howe Lab, University of Iowa Hospital and Clinics

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	2.0
DANN	Benign	0.19
DEOGEN2	Benign	0.021	T;T;T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.034	N
MetaRNN	Benign	0.0089	T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L;L;L;L;L
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PROVEAN	Uncertain	-3.0	D;D;.;D;D
REVEL	Benign	0.017
Sift	Benign	0.11	T;T;.;T;T
Sift4G	Uncertain	0.059	T;T;T;T;T
Polyphen		0.11	B;B;B;B;B
Vest4		0.21
MutPred		0.31		Gain of catalytic residue at H275 (P = 0.0733);Gain of catalytic residue at H275 (P = 0.0733);Gain of catalytic residue at H275 (P = 0.0733);Gain of catalytic residue at H275 (P = 0.0733);Gain of catalytic residue at H275 (P = 0.0733);
MVP		0.19
MPC		0.13
ClinPred		0.16	T
GERP RS		-1.6
Varity_R		0.12
gMVP		0.25

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

LitVar

Other links and lift over

dbSNP: rs575275768; hg19: chr19-53116994;