16-88432736-G-T

Position:

• chr16-88432736-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001367624.2(ZNF469):​c.5266G>T​(p.Ala1756Ser) 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. 13/18 in silico tools predict 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: ZNF469 NM_001367624.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.20

Genes affected

ZNF469 (HGNC:23216): (zinc finger protein 469) This gene encodes a zinc-finger protein. Low-percent homology to certain collagens suggests that it may function as a transcription factor or extra-nuclear regulator factor for the synthesis or organization of collagen fibers. Mutations in this gene cause brittle cornea syndrome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042179793).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF469	NM_001367624.2	c.5266G>T	p.Ala1756Ser	missense_variant	3/3	ENST00000565624.3	NP_001354553.1
ZNF469	XM_047434810.1	c.5266G>T	p.Ala1756Ser	missense_variant	4/4		XP_047290766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF469	ENST00000565624.3	c.5266G>T	p.Ala1756Ser	missense_variant	3/3		NM_001367624.2	ENSP00000456500	A2
ZNF469	ENST00000437464.1	c.5182G>T	p.Ala1728Ser	missense_variant	2/2	5		ENSP00000402343	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 95

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.0040
DANN	Benign	0.66
DEOGEN2	Benign	0.0018	T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.34	T;.
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.042	T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	0.15	N;N
REVEL	Benign	0.013
Sift	Benign	0.91	T;T
Sift4G	Benign	0.55	T;T
Vest4		0.068
MutPred		0.18		.;Gain of phosphorylation at A1728 (P = 0.0056);
MVP		0.15
ClinPred		0.051	T
GERP RS		-4.9
gMVP		0.0062

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

Publications

LitVar

Other links and lift over

dbSNP: rs371328036; hg19: chr16-88499144;