9-101408158-C-T

Variant names:

• chr9-101408158-C-T
• rs1830782098
• NM_003452.4:c.390C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003452.4(ZNF189):​c.390C>T​(p.Phe130Phe) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF189 NM_003452.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.503
• Publications: 0 publications found

Genes affected

ZNF189 (HGNC:12980): (zinc finger protein 189) Kruppel-like zinc finger proteins such as ZNF189 contain a conserved stretch of 7 amino acids that connects a variable number of DNA-binding zinc finger repeats of the cys(2)his(2) (C2H2) type (summarized by Odeberg et al., 1998 [PubMed 9653648]). Approximately 30% of human Kruppel-like zinc finger proteins contain an N-terminal Kruppel-associated box (KRAB) domain. The KRAB domain consists of approximately 75 amino acids that may be subdivided into an A box, which is present in every KRAB domain and is essential for transcriptional repression, and a B box, which is not always present.[supplied by OMIM, May 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=-0.503 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003452.4. 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
	ZNF189	NM_003452.4	MANE Select	c.390C>T	p.Phe130Phe	synonymous	Exon 3 of 3	NP_003443.2
	ZNF189	NM_001278231.2		c.348C>T	p.Phe116Phe	synonymous	Exon 3 of 3	NP_001265160.1	O75820-2
	ZNF189	NM_001278232.2		c.345C>T	p.Phe115Phe	synonymous	Exon 3 of 3	NP_001265161.1	B7ZLK9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF189	ENST00000339664.7	TSL:1 MANE Select	c.390C>T	p.Phe130Phe	synonymous	Exon 3 of 3	ENSP00000342019.2	O75820-1
	ZNF189	ENST00000374861.7	TSL:1	c.348C>T	p.Phe116Phe	synonymous	Exon 3 of 3	ENSP00000363995.3	O75820-2
	ZNF189	ENST00000259395.4	TSL:1	c.264C>T	p.Phe88Phe	synonymous	Exon 4 of 4	ENSP00000259395.4	O75820-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	5.2
DANN	Benign	0.62
PhyloP100		-0.50

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: rs1830782098; hg19: chr9-104170440;