rs12236219

Variant names:

• chr9-94300699-C-T
• rs12236219
• NM_194320.4:c.1141C>T

Variant summary

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

The NM_194320.4(ZNF169):​c.1141C>T​(p.Arg381Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0679 in 1,613,872 control chromosomes in the GnomAD database, including 7,717 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.084 (994 hom., cov: 33)
  • Exomes 𝑓: 0.066 (6723 hom.)
• Consequence: ZNF169 NM_194320.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26

Genes affected

ZNF169 (HGNC:12957): (zinc finger protein 169) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located 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=0.005741477).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF169	NM_194320.4	c.1141C>T	p.Arg381Cys	missense_variant	Exon 5 of 5	ENST00000395395.7	NP_919301.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF169	ENST00000395395.7	c.1141C>T	p.Arg381Cys	missense_variant	Exon 5 of 5	2	NM_194320.4	ENSP00000378792.2
ZNF169	ENST00000340911.8	c.*1130C>T		3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000340711.4

Frequencies

GnomAD3 genomes AF: 0.0835 AC: 12694 AN: 151944 Hom.: 995 Cov.: 33

Gnomad AFR AF: 0.0810

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.0550

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0387

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0445

Gnomad OTH AF: 0.0914

GnomAD3 exomes AF: 0.118 AC: 29740 AN: 251036 Hom.: 3470 AF XY: 0.110 AC XY: 14937 AN XY: 135684

Gnomad AFR exome AF: 0.0811

Gnomad AMR exome AF: 0.296

Gnomad ASJ exome AF: 0.0604

Gnomad EAS exome AF: 0.377

Gnomad SAS exome AF: 0.135

Gnomad FIN exome AF: 0.0436

Gnomad NFE exome AF: 0.0447

Gnomad OTH exome AF: 0.0839

GnomAD4 exome AF: 0.0662 AC: 96844 AN: 1461808 Hom.: 6723 Cov.: 34 AF XY: 0.0671 AC XY: 48829 AN XY: 727212

Gnomad4 AFR exome AF: 0.0790

Gnomad4 AMR exome AF: 0.285

Gnomad4 ASJ exome AF: 0.0619

Gnomad4 EAS exome AF: 0.337

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.0440

Gnomad4 NFE exome AF: 0.0426

Gnomad4 OTH exome AF: 0.0819

GnomAD4 genome AF: 0.0836 AC: 12706 AN: 152064 Hom.: 994 Cov.: 33 AF XY: 0.0883 AC XY: 6564 AN XY: 74338

Gnomad4 AFR AF: 0.0809

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.0550

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.0387

Gnomad4 NFE AF: 0.0445

Gnomad4 OTH AF: 0.0927

Alfa AF: 0.0612 Hom.: 1381

Bravo AF: 0.0974

TwinsUK AF: 0.0372 AC: 138

ALSPAC AF: 0.0423 AC: 163

ESP6500AA AF: 0.0788 AC: 347

ESP6500EA AF: 0.0442 AC: 380

ExAC AF: 0.109 AC: 13268

Asia WGS AF: 0.250 AC: 866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.75	T
MetaRNN	Benign	0.0057	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-6.4	D
REVEL	Benign	0.056
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.14
MPC		0.38
ClinPred		0.056	T
GERP RS		0.85
Varity_R		0.33
gMVP		0.16

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: rs12236219; hg19: chr9-97062981; COSMIC: COSV61763433; COSMIC: COSV61763433;