rs978091102

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024741.3(ZNF408):​c.46C>G​(p.Gln16Glu) 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. 14/20 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

ZNF408
NM_024741.3 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0540
Variant links:
Genes affected
ZNF408 (HGNC:20041): (zinc finger protein 408) The protein encoded by this gene contains ten tandem zinc fingers and an N-terminal SET domain, so it is likely a DNA binding protein that interacts with other proteins. In adults, the encoded protein is expressed most highly in retina. Consequently, defects in this gene have been associated with familial exudative vitreoretinopathy (FEVR) and retinitis pigmentosa (RP). [provided by RefSeq, Dec 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.05737269).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF408NM_024741.3 linkc.46C>G p.Gln16Glu missense_variant Exon 1 of 5 ENST00000311764.3 NP_079017.1 Q9H9D4
ZNF408NM_001184751.2 linkc.-21C>G 5_prime_UTR_variant Exon 1 of 5 NP_001171680.1 Q9H9D4B4DXY4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF408ENST00000311764.3 linkc.46C>G p.Gln16Glu missense_variant Exon 1 of 5 1 NM_024741.3 ENSP00000309606.2 Q9H9D4
ZNF408ENST00000526410.1 linkn.63C>G non_coding_transcript_exon_variant Exon 1 of 3 3
ZNF408ENST00000531866.1 linkn.64C>G non_coding_transcript_exon_variant Exon 1 of 2 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
6.2
DANN
Benign
0.76
DEOGEN2
Benign
0.022
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.0016
N
LIST_S2
Benign
0.44
T
M_CAP
Benign
0.0043
T
MetaRNN
Benign
0.057
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.90
L
PROVEAN
Benign
-0.20
N
REVEL
Benign
0.091
Sift
Benign
0.090
T
Sift4G
Benign
0.23
T
Polyphen
0.0010
B
Vest4
0.13
MutPred
0.12
Gain of helix (P = 0.0696);
MVP
0.067
MPC
0.20
ClinPred
0.11
T
GERP RS
-0.69
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.096
gMVP
0.23

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs978091102; hg19: chr11-46722643; API