9-94300150-G-T

Variant names:

• chr9-94300150-G-T
• NM_194320.4:c.592G>T

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.592G>T​(p.Asp198Tyr) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF169 NM_194320.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.88
• Publications: 0 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=0.24429935).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF169	NM_194320.4	c.592G>T	p.Asp198Tyr	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.592G>T	p.Asp198Tyr	missense_variant	Exon 5 of 5	2	NM_194320.4	ENSP00000378792.2
ZNF169	ENST00000718459.1	c.595G>T	p.Asp199Tyr	missense_variant	Exon 5 of 5			ENSP00000520837.1
ZNF169	ENST00000340911.8	c.*581G>T		3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000340711.4
ZNF169	ENST00000718460.1	c.*329G>T		downstream_gene_variant				ENSP00000520838.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 16, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.592G>T (p.D198Y) alteration is located in exon 5 (coding exon 4) of the ZNF169 gene. This alteration results from a G to T substitution at nucleotide position 592, causing the aspartic acid (D) at amino acid position 198 to be replaced by a tyrosine (Y). 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	0.095
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.9
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.059
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.025	D
Polyphen		0.99	D
Vest4		0.39
MutPred		0.38		Loss of disorder (P = 0.0205);
MVP		0.26
MPC		0.10
ClinPred		0.60	D
GERP RS		2.4
Varity_R		0.28
gMVP		0.12
Mutation Taster		=99/1	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

hg19: chr9-97062432;