19-44327836-T-G

Variant names:

• chr19-44327836-T-G
• rs2609881
• NM_013380.4:c.2321A>C

Variant summary

Our verdict is Benign. The variant received -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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 25 publications found

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]

ZNF112 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013380.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF112	NM_013380.4	MANE Select	c.2321A>C	p.Glu774Ala	missense	Exon 4 of 4	NP_037512.3
	ZNF112	NM_001348281.2		c.2390A>C	p.Glu797Ala	missense	Exon 5 of 5	NP_001335210.1
	ZNF112	NM_001083335.2		c.2339A>C	p.Glu780Ala	missense	Exon 5 of 5	NP_001076804.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF112	ENST00000354340.9	TSL:1 MANE Select	c.2321A>C	p.Glu774Ala	missense	Exon 4 of 4	ENSP00000346305.3
	ZNF112	ENST00000337401.8	TSL:1	c.2339A>C	p.Glu780Ala	missense	Exon 5 of 5	ENSP00000337081.3

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

GnomAD2 exomes AF: 0.181 AC: 45404 AN: 251336 AF XY: 0.167

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 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

African (AFR) AF: 0.439 AC: 14696 AN: 33470

American (AMR) AF: 0.328 AC: 14665 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 5177 AN: 26134

East Asian (EAS) AF: 0.167 AC: 6631 AN: 39700

South Asian (SAS) AF: 0.119 AC: 10284 AN: 86258

European-Finnish (FIN) AF: 0.135 AC: 7204 AN: 53420

Middle Eastern (MID) AF: 0.225 AC: 1298 AN: 5764

European-Non Finnish (NFE) AF: 0.122 AC: 135536 AN: 1111978

Other (OTH) AF: 0.160 AC: 9642 AN: 60396

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

African (AFR) AF: 0.432 AC: 17906 AN: 41432

American (AMR) AF: 0.293 AC: 4474 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 674 AN: 3462

East Asian (EAS) AF: 0.165 AC: 851 AN: 5170

South Asian (SAS) AF: 0.111 AC: 535 AN: 4826

European-Finnish (FIN) AF: 0.141 AC: 1494 AN: 10590

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8091 AN: 68008

Other (OTH) AF: 0.220 AC: 464 AN: 2108

Alfa AF: 0.164 Hom.: 8828

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 v4.9

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
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.047	T
MetaRNN	Benign	0.00021	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.52	N
PhyloP100		-1.8
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.042
Sift	Benign	0.24	T
Sift4G	Benign	0.36	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
Mutation Taster		=98/2	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: rs2609881; hg19: chr19-44831989; COSMIC: COSV61619815; COSMIC: COSV61619815;