19-44327836-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013380.4(ZNF112):c.2321A>C(p.Glu774Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,613,910 control chromosomes in the GnomAD database, including 22,548 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (5379 hom., cov: 32)
  • Exomes 𝑓: 0.14 (17169 hom.)
• Consequence: ZNF112 NM_013380.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

Genes affected

ZNF112 (HGNC:12892): (zinc finger protein 112) 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.0799041E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF112	NM_013380.4	c.2321A>C	p.Glu774Ala	missense_variant	4/4	ENST00000354340.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF112	ENST00000354340.9	c.2321A>C	p.Glu774Ala	missense_variant	4/4	1	NM_013380.4	A2
ZNF112	ENST00000337401.8	c.2339A>C	p.Glu780Ala	missense_variant	5/5	1		P4

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34596 AN: 151962 Hom.: 5359 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.215

GnomAD3 exomes AF: 0.181 AC: 45404 AN: 251336 Hom.: 5427 AF XY: 0.167 AC XY: 22702 AN XY: 135838

Gnomad AFR exome AF: 0.437

Gnomad AMR exome AF: 0.339

Gnomad ASJ exome AF: 0.196

Gnomad EAS exome AF: 0.159

Gnomad SAS exome AF: 0.113

Gnomad FIN exome AF: 0.136

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.170

GnomAD4 exome AF: 0.140 AC: 205133 AN: 1461830 Hom.: 17169 Cov.: 32 AF XY: 0.139 AC XY: 100884 AN XY: 727228

Gnomad4 AFR exome AF: 0.439

Gnomad4 AMR exome AF: 0.328

Gnomad4 ASJ exome AF: 0.198

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.119

Gnomad4 FIN exome AF: 0.135

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome AF: 0.228 AC: 34671 AN: 152080 Hom.: 5379 Cov.: 32 AF XY: 0.230 AC XY: 17094 AN XY: 74352

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.220

Alfa AF: 0.148 Hom.: 4928

Bravo AF: 0.254

TwinsUK AF: 0.110 AC: 409

ALSPAC AF: 0.124 AC: 479

ESP6500AA AF: 0.426 AC: 1877

ESP6500EA AF: 0.125 AC: 1078

ExAC AF: 0.176 AC: 21316

Asia WGS AF: 0.176 AC: 614 AN: 3478

EpiCase AF: 0.128

EpiControl AF: 0.137

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	17
Dann	Benign	0.94
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.047	T;T
MetaRNN	Benign	0.00021	T;T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Benign	0.042
Sift	Benign	0.24	T;T
Sift4G	Benign	0.36	T;T
Polyphen		0.0030	.;B
Vest4		0.059
MPC		0.13
ClinPred		0.0047	T
GERP RS		1.7
Varity_R		0.24
gMVP		0.10

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: rs2609881; hg19: chr19-44831989; COSMIC: COSV61619815; COSMIC: COSV61619815;