NM_013380.4:c.2321A>G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013380.4(ZNF112):​c.2321A>G​(p.Glu774Gly) 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. 14/21 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: not found (cov: 32)
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07874581).

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>G	p.Glu774Gly	missense	Exon 4 of 4	NP_037512.3
	ZNF112	NM_001348281.2		c.2390A>G	p.Glu797Gly	missense	Exon 5 of 5	NP_001335210.1
	ZNF112	NM_001083335.2		c.2339A>G	p.Glu780Gly	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>G	p.Glu774Gly	missense	Exon 4 of 4	ENSP00000346305.3
	ZNF112	ENST00000337401.8	TSL:1	c.2339A>G	p.Glu780Gly	missense	Exon 5 of 5	ENSP00000337081.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251336 AF XY: 0.00

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: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.30	N
PhyloP100		-1.8
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.023
Sift	Benign	0.24	T
Sift4G	Benign	0.24	T
Polyphen		0.33	B
Vest4		0.13
MVP		0.13
MPC		0.36
ClinPred		0.18	T
GERP RS		1.7
Varity_R		0.20
gMVP		0.088
Mutation Taster		=98/2	polymorphism

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;