20-50891491-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001282531.3(ADNP):c.3223G>A(p.Glu1075Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ADNP NM_001282531.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.45

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]

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=0.22589391).
• BP6: Variant 20-50891491-C-T is Benign according to our data. Variant chr20-50891491-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2014672.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADNP	NM_001282531.3	c.3223G>A	p.Glu1075Lys	missense_variant	6/6	ENST00000621696.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADNP	ENST00000621696.5	c.3223G>A	p.Glu1075Lys	missense_variant	6/6	5	NM_001282531.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460136 Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2 AN XY: 726480

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 13, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T;T;T;T;.
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.23	T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.34	N;N;N;N;N;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.33	N;.;N;N;N;.
REVEL	Benign	0.19
Sift	Uncertain	0.011	D;.;D;D;D;.
Sift4G	Benign	0.10	T;T;T;T;T;.
Polyphen		0.32	B;B;B;B;B;.
Vest4		0.18
MutPred		0.15		Gain of ubiquitination at E1075 (P = 0.0042);Gain of ubiquitination at E1075 (P = 0.0042);Gain of ubiquitination at E1075 (P = 0.0042);Gain of ubiquitination at E1075 (P = 0.0042);Gain of ubiquitination at E1075 (P = 0.0042);.;
MVP		0.45
ClinPred		0.73	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-49508028;