19-9413706-G-T

Variant names:

• chr19-9413706-G-T
• rs760017788
• NM_001370374.1:c.1420C>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.1420C>A​(p.Pro474Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P474S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF266 NM_001370374.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.71
• 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=0.2061249).

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.1420C>A	p.Pro474Thr	missense	Exon 11 of 11	NP_001357303.1	A0A3F2YPB8
	ZNF266	NM_001370375.1		c.1420C>A	p.Pro474Thr	missense	Exon 11 of 11	NP_001357304.1	A0A3F2YPB8
	ZNF266	NM_001370384.1		c.1420C>A	p.Pro474Thr	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.1420C>A	p.Pro474Thr	missense	Exon 11 of 11	ENSP00000466714.2	A0A3F2YPB8
	ZNF266	ENST00000588933.5	TSL:1	c.1219C>A	p.Pro407Thr	missense	Exon 11 of 11	ENSP00000467151.1	Q14584
	ZNF266	ENST00000590306.5	TSL:1	c.1219C>A	p.Pro407Thr	missense	Exon 10 of 10	ENSP00000467315.1	Q14584

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461852 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727226

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

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.7
PrimateAI	Benign	0.35	T
Sift4G	Uncertain	0.010	D
Polyphen		0.49	P
Vest4		0.14
MutPred		0.46		Loss of catalytic residue at P407 (P = 0.0394)
MVP		0.33
MPC		0.23
ClinPred		0.89	D
GERP RS		-0.90
Varity_R		0.44
Mutation Taster		=88/12	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: rs760017788; hg19: chr19-9524382;