rs587777524

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001282531.3(ADNP):​c.1211C>T​(p.Ser404Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,461,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ADNP
NM_001282531.3 missense

Scores

1
3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.36
Variant links:
Genes affected
ADNP (HGNC:15766): (activity dependent neuroprotector homeobox) Vasoactive intestinal peptide is a neuroprotective factor that has a stimulatory effect on the growth of some tumor cells and an inhibitory effect on others. This gene encodes a protein that is upregulated by vasoactive intestinal peptide and may be involved in its stimulatory effect on certain tumor cells. The encoded protein contains one homeobox and nine zinc finger domains, suggesting that it functions as a transcription factor. This gene is also upregulated in normal proliferative tissues. Finally, the encoded protein may increase the viability of certain cell types through modulation of p53 activity. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.18933055).
BS2
High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ADNPNM_001282531.3 linkuse as main transcriptc.1211C>T p.Ser404Leu missense_variant 6/6 ENST00000621696.5 NP_001269460.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ADNPENST00000621696.5 linkuse as main transcriptc.1211C>T p.Ser404Leu missense_variant 6/65 NM_001282531.3 ENSP00000483881 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
250992
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135674
show subpopulations
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:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000116
AC:
17
AN:
1461474
Hom.:
0
Cov.:
34
AF XY:
0.0000110
AC XY:
8
AN XY:
727074
show subpopulations
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000135
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.097
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
23
DANN
Benign
0.97
DEOGEN2
Benign
0.11
T;T;T;T;T;.
Eigen
Benign
0.18
Eigen_PC
Uncertain
0.28
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Pathogenic
0.98
.;D;.;.;.;D
M_CAP
Benign
0.0026
T
MetaRNN
Benign
0.19
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;N;N;N;N;.
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-0.81
N;.;N;N;N;.
REVEL
Benign
0.12
Sift
Benign
0.29
T;.;T;T;T;.
Sift4G
Uncertain
0.034
D;D;D;D;D;.
Polyphen
0.72
P;P;P;P;P;.
Vest4
0.22
MutPred
0.18
Loss of phosphorylation at S404 (P = 0.0151);Loss of phosphorylation at S404 (P = 0.0151);Loss of phosphorylation at S404 (P = 0.0151);Loss of phosphorylation at S404 (P = 0.0151);Loss of phosphorylation at S404 (P = 0.0151);.;
MVP
0.47
ClinPred
0.36
T
GERP RS
6.2
Varity_R
0.082
gMVP
0.50

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: rs587777524; hg19: chr20-49510040; API