rs77951481

chr16-88430187-C-Gchr16-88430187-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001367624.2(ZNF469):c.2717C>G(p.Pro906Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000358 in 1,395,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P906L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: ZNF469 NM_001367624.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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]

LOC112268182 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22173667).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF469	NM_001367624.2	c.2717C>G	p.Pro906Arg	missense_variant	3/3	ENST00000565624.3
LOC112268182	XR_007065178.1	n.92-65G>C		intron_variant, non_coding_transcript_variant
ZNF469	XM_047434810.1	c.2717C>G	p.Pro906Arg	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF469	ENST00000565624.3	c.2717C>G	p.Pro906Arg	missense_variant	3/3		NM_001367624.2	A2
ZNF469	ENST00000437464.1	c.2717C>G	p.Pro906Arg	missense_variant	1/2	5		P4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000694 AC: 1 AN: 144094 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 77926

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000188

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000358 AC: 5 AN: 1395462 Hom.: 0 Cov.: 65 AF XY: 0.00 AC XY: 0 AN XY: 687896

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000464

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	2.2
Dann	Uncertain	0.98
DEOGEN2	Benign	0.021	T;.
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.31	T;.
M_CAP	Pathogenic	0.91	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.9	N;N
Sift	Benign	0.11	T;T
Sift4G	Uncertain	0.014	D;D
Vest4		0.20
MutPred		0.14		Loss of glycosylation at P906 (P = 0.0395);Loss of glycosylation at P906 (P = 0.0395);
MVP		0.31
ClinPred		0.15	T
GERP RS		-0.48
gMVP		0.065

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: rs77951481; hg19: chr16-88496595;