chr19-44327931-C-T

Variant names:

• chr19-44327931-C-T
• rs61733035
• NM_013380.4:c.2226G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_013380.4(ZNF112):​c.2226G>A​(p.Pro742Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,609,758 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0089 (20 hom., cov: 32)
  • Exomes 𝑓: 0.00089 (18 hom.)
• Consequence: ZNF112 NM_013380.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.57
• Publications: 0 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 19-44327931-C-T is Benign according to our data. Variant chr19-44327931-C-T is described in ClinVar as Benign. ClinVar VariationId is 769019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.57 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00887 (1312/147982) while in subpopulation AFR AF = 0.0307 (1232/40124). AF 95% confidence interval is 0.0293. There are 20 homozygotes in GnomAd4. There are 628 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 20 Unknown gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF112	NM_013380.4	MANE Select	c.2226G>A	p.Pro742Pro	synonymous	Exon 4 of 4	NP_037512.3
	ZNF112	NM_001348281.2		c.2295G>A	p.Pro765Pro	synonymous	Exon 5 of 5	NP_001335210.1
	ZNF112	NM_001083335.2		c.2244G>A	p.Pro748Pro	synonymous	Exon 5 of 5	NP_001076804.1	Q9UJU3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF112	ENST00000354340.9	TSL:1 MANE Select	c.2226G>A	p.Pro742Pro	synonymous	Exon 4 of 4	ENSP00000346305.3	Q9UJU3-2
	ZNF112	ENST00000337401.8	TSL:1	c.2244G>A	p.Pro748Pro	synonymous	Exon 5 of 5	ENSP00000337081.3	Q9UJU3-1
	ZNF112	ENST00000911245.1		c.2226G>A	p.Pro742Pro	synonymous	Exon 5 of 5	ENSP00000581304.1

Frequencies

GnomAD3 genomes AF: 0.00885 AC: 1308 AN: 147858 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.0307

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00403

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000135

Gnomad OTH AF: 0.00549

GnomAD2 exomes AF: 0.00212 AC: 531 AN: 250972 AF XY: 0.00163

Gnomad AFR exome AF: 0.0287

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.000654

GnomAD4 exome AF: 0.000895 AC: 1308 AN: 1461776 Hom.: 18 Cov.: 31 AF XY: 0.000796 AC XY: 579 AN XY: 727192

African (AFR) AF: 0.0303 AC: 1013 AN: 33468

American (AMR) AF: 0.00123 AC: 55 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.000109 AC: 121 AN: 1111934

Other (OTH) AF: 0.00176 AC: 106 AN: 60390

GnomAD4 genome AF: 0.00887 AC: 1312 AN: 147982 Hom.: 20 Cov.: 32 AF XY: 0.00868 AC XY: 628 AN XY: 72330

African (AFR) AF: 0.0307 AC: 1232 AN: 40124

American (AMR) AF: 0.00403 AC: 60 AN: 14896

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3426

East Asian (EAS) AF: 0.00 AC: 0 AN: 4828

South Asian (SAS) AF: 0.00 AC: 0 AN: 4560

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 230

European-Non Finnish (NFE) AF: 0.000135 AC: 9 AN: 66676

Other (OTH) AF: 0.00543 AC: 11 AN: 2026

Alfa AF: 0.00446 Hom.: 7

Bravo AF: 0.00917

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.1
DANN	Benign	0.62
PhyloP100		-3.6
Mutation Taster		=100/0	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: rs61733035; hg19: chr19-44832084; COSMIC: COSV105222940; COSMIC: COSV105222940;