8-24397341-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_014479.3(ADAMDEC1):​c.512C>A​(p.Ala171Asp) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ADAMDEC1
NM_014479.3 missense

Scores

4
3
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.497
Variant links:
Genes affected
ADAMDEC1 (HGNC:16299): (ADAM like decysin 1) This encoded protein is thought to be a secreted protein belonging to the disintegrin metalloproteinase family. Its expression is upregulated during dendritic cells maturation. This protein may play an important role in dendritic cell function and their interactions with germinal center T cells. [provided by RefSeq, Jul 2008]
ADAM7-AS1 (HGNC:56152): (ADAM7, ADAMDEC1 and ADAM28 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.91

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ADAMDEC1NM_014479.3 linkuse as main transcriptc.512C>A p.Ala171Asp missense_variant 6/14 ENST00000256412.8 NP_055294.1
ADAM7-AS1NR_125808.1 linkuse as main transcriptn.80-9350G>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ADAMDEC1ENST00000256412.8 linkuse as main transcriptc.512C>A p.Ala171Asp missense_variant 6/141 NM_014479.3 ENSP00000256412 P1O15204-1
ADAM7-AS1ENST00000519689.1 linkuse as main transcriptn.185-9350G>T intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250848
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135572
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 11, 2022The c.512C>A (p.A171D) alteration is located in exon 6 (coding exon 6) of the ADAMDEC1 gene. This alteration results from a C to A substitution at nucleotide position 512, causing the alanine (A) at amino acid position 171 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.33
BayesDel_addAF
Benign
0.0082
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
17
DANN
Uncertain
1.0
DEOGEN2
Benign
0.061
T;.
Eigen
Uncertain
0.23
Eigen_PC
Benign
0.023
FATHMM_MKL
Benign
0.27
N
LIST_S2
Benign
0.49
T;T
M_CAP
Benign
0.011
T
MetaRNN
Pathogenic
0.91
D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
3.4
M;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.33
T
PROVEAN
Pathogenic
-5.4
D;D
REVEL
Benign
0.12
Sift
Uncertain
0.0010
D;D
Sift4G
Pathogenic
0.0010
D;D
Polyphen
1.0
D;.
Vest4
0.88
MutPred
0.66
Gain of ubiquitination at K168 (P = 0.0851);.;
MVP
0.52
MPC
0.41
ClinPred
0.95
D
GERP RS
2.8
Varity_R
0.96
gMVP
0.90

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs766090181; hg19: chr8-24254854; API