19-21405837-T-G

Position:

• chr19-21405837-T-G

Variant summary

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

The ENST00000392288.7(ZNF493):​c.234T>G​(p.Ser78Arg) 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. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF493 ENST00000392288.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.39

Genes affected

ZNF493 (HGNC:23708): (zinc finger protein 493) Predicted to enable DNA-binding transcription activator 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 active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.057894975).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF493	NM_001076678.3	c.234T>G	p.Ser78Arg	missense_variant	3/4	ENST00000392288.7	NP_001070146.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF493	ENST00000392288.7	c.234T>G	p.Ser78Arg	missense_variant	3/4	1	NM_001076678.3	ENSP00000376110	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000210 AC: 3 AN: 1431012 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 711930

Gnomad4 AFR exome AF: 0.0000617

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.14e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 07, 2022

The c.234T>G (p.S78R) alteration is located in exon 3 (coding exon 3) of the ZNF493 gene. This alteration results from a T to G substitution at nucleotide position 234, causing the serine (S) at amino acid position 78 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.3
DANN	Benign	0.66
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.28	T;T;T;T
M_CAP	Benign	0.00091	T
MetaRNN	Benign	0.058	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.17	.;N;.;N
REVEL	Benign	0.016
Sift	Benign	0.32	.;T;.;D
Sift4G	Benign	0.082	T;T;T;D
Polyphen		0.96	.;D;.;.
Vest4		0.11
MutPred		0.30		.;Loss of ubiquitination at K75 (P = 0.0347);Loss of ubiquitination at K75 (P = 0.0347);.;
MVP		0.072
MPC		0.018
ClinPred		0.12	T
GERP RS		-2.3
gMVP		0.011

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: chr19-21588639;