chr19-9413310-C-T

Variant names:

• chr19-9413310-C-T
• NM_001370374.1:c.1816G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001370374.1(ZNF266):​c.1816G>A​(p.Glu606Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,450,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 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)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: ZNF266 NM_001370374.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.27
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050332814).

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.1816G>A	p.Glu606Lys	missense	Exon 11 of 11	NP_001357303.1	A0A3F2YPB8
	ZNF266	NM_001370375.1		c.1816G>A	p.Glu606Lys	missense	Exon 11 of 11	NP_001357304.1	A0A3F2YPB8
	ZNF266	NM_001370384.1		c.1816G>A	p.Glu606Lys	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.1816G>A	p.Glu606Lys	missense	Exon 11 of 11	ENSP00000466714.2	A0A3F2YPB8
	ZNF266	ENST00000588933.5	TSL:1	c.1615G>A	p.Glu539Lys	missense	Exon 11 of 11	ENSP00000467151.1	Q14584
	ZNF266	ENST00000590306.5	TSL:1	c.1615G>A	p.Glu539Lys	missense	Exon 10 of 10	ENSP00000467315.1	Q14584

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000276 AC: 4 AN: 1450484 Hom.: 0 Cov.: 29 AF XY: 0.00000555 AC XY: 4 AN XY: 720462

African (AFR) AF: 0.00 AC: 0 AN: 33100

American (AMR) AF: 0.00 AC: 0 AN: 43450

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25318

East Asian (EAS) AF: 0.00 AC: 0 AN: 39572

South Asian (SAS) AF: 0.00 AC: 0 AN: 84656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53098

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5696

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1105740

Other (OTH) AF: 0.0000167 AC: 1 AN: 59854

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	Benign	0.16
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	9.7
DANN	Benign	0.83
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.000040	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.27	N
PhyloP100		-2.3
PrimateAI	Benign	0.25	T
Sift4G	Benign	0.13	T
Polyphen		0.0010	B
Vest4		0.090
MutPred		0.37		Gain of MoRF binding (P = 0.0023)
MVP		0.20
MPC		0.030
ClinPred		0.046	T
GERP RS		-4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.032
Mutation Taster		=100/0	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: chr19-9523986;