rs752987255

Variant names:

• chr9-94300276-G-A
• rs752987255
• NM_194320.4:c.718G>A

Variant summary

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

The NM_194320.4(ZNF169):​c.718G>A​(p.Gly240Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000589 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: ZNF169 NM_194320.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.27
• Publications: 2 publications found

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

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=0.19737503).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF169	NM_194320.4	c.718G>A	p.Gly240Arg	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.718G>A	p.Gly240Arg	missense_variant	Exon 5 of 5	2	NM_194320.4	ENSP00000378792.2
ZNF169	ENST00000718459.1	c.721G>A	p.Gly241Arg	missense_variant	Exon 5 of 5			ENSP00000520837.1
ZNF169	ENST00000340911.8	c.*707G>A		3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000340711.4

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152190 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000995 AC: 25 AN: 251280 AF XY: 0.000110

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00119

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000568 AC: 83 AN: 1461888 Hom.: 0 Cov.: 33 AF XY: 0.0000633 AC XY: 46 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00122 AC: 32 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000360 AC: 40 AN: 1112012

Other (OTH) AF: 0.000132 AC: 8 AN: 60396

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152190 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74354

African (AFR) AF: 0.0000241 AC: 1 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68028

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.000203 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.0000741 AC: 9

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.718G>A (p.G240R) alteration is located in exon 5 (coding exon 4) of the ZNF169 gene. This alteration results from a G to A substitution at nucleotide position 718, causing the glycine (G) at amino acid position 240 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.085	T
Eigen	Uncertain	0.33
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.3
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Benign	0.28
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.30
MutPred		0.78		Gain of MoRF binding (P = 0.0718);
MVP		0.43
MPC		0.48
ClinPred		0.54	D
GERP RS		2.6
Varity_R		0.28
gMVP		0.12
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs752987255; hg19: chr9-97062558; COSMIC: COSV61763016; COSMIC: COSV61763016;