19-9413535-A-T

Variant names:

• chr19-9413535-A-T
• rs754636084
• NM_001370374.1:c.1591T>A

Variant summary

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

The NM_001370374.1(ZNF266):​c.1591T>A​(p.Phe531Ile) 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. 12/19 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: ZNF266 NM_001370374.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.06
• Publications: 0 publications found

Genes affected

ZNF266 (HGNC:13059): (zinc finger protein 266) This gene encodes a protein containing many tandem zinc-finger motifs. Zinc fingers are protein or nucleic acid-binding domains, and may be involved in a variety of functions, including regulation of transcription. This gene is located in a cluster of similar genes encoding zinc finger proteins on chromosome 19. Alternative splicing results in multiple transcript variants for this gene. [provided by RefSeq, Sep 2012]

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=0.12376997).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370374.1. 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
	ZNF266	NM_001370374.1	MANE Select	c.1591T>A	p.Phe531Ile	missense	Exon 11 of 11	NP_001357303.1	A0A3F2YPB8
	ZNF266	NM_001370375.1		c.1591T>A	p.Phe531Ile	missense	Exon 11 of 11	NP_001357304.1	A0A3F2YPB8
	ZNF266	NM_001370384.1		c.1591T>A	p.Phe531Ile	missense	Exon 10 of 10	NP_001357313.1	A0A3F2YPB8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF266	ENST00000592904.7	TSL:1 MANE Select	c.1591T>A	p.Phe531Ile	missense	Exon 11 of 11	ENSP00000466714.2	A0A3F2YPB8
	ZNF266	ENST00000588933.5	TSL:1	c.1390T>A	p.Phe464Ile	missense	Exon 11 of 11	ENSP00000467151.1	Q14584
	ZNF266	ENST00000590306.5	TSL:1	c.1390T>A	p.Phe464Ile	missense	Exon 10 of 10	ENSP00000467315.1	Q14584

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.00061	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.1
PrimateAI	Benign	0.32	T
Sift4G	Uncertain	0.010	D
Polyphen		0.16	B
Vest4		0.14
MutPred		0.58		Loss of disorder (P = 0.1164)
MVP		0.055
MPC		0.095
ClinPred		0.78	D
GERP RS		1.9
Varity_R		0.35
Mutation Taster		=87/13	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: rs754636084; hg19: chr19-9524211;