chr8-24394146-T-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014479.3(ADAMDEC1):​c.362T>C​(p.Met121Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00489 in 1,607,606 control chromosomes in the GnomAD database, including 340 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.026 ( 164 hom., cov: 32)
Exomes 𝑓: 0.0027 ( 176 hom. )

Consequence

ADAMDEC1
NM_014479.3 missense, splice_region

Scores

18
Splicing: ADA: 0.00001287
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.361
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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.00237903).
BP6
Variant 8-24394146-T-C is Benign according to our data. Variant chr8-24394146-T-C is described in ClinVar as [Benign]. Clinvar id is 781121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.088 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADAMDEC1NM_014479.3 linkc.362T>C p.Met121Thr missense_variant, splice_region_variant Exon 4 of 14 ENST00000256412.8 NP_055294.1 O15204-1B7Z6V5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADAMDEC1ENST00000256412.8 linkc.362T>C p.Met121Thr missense_variant, splice_region_variant Exon 4 of 14 1 NM_014479.3 ENSP00000256412.4 O15204-1

Frequencies

GnomAD3 genomes
AF:
0.0257
AC:
3914
AN:
152140
Hom.:
162
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0902
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00792
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000309
Gnomad OTH
AF:
0.0153
GnomAD2 exomes
AF:
0.00682
AC:
1710
AN:
250712
AF XY:
0.00505
show subpopulations
Gnomad AFR exome
AF:
0.0946
Gnomad AMR exome
AF:
0.00333
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000229
Gnomad OTH exome
AF:
0.00393
GnomAD4 exome
AF:
0.00270
AC:
3928
AN:
1455348
Hom.:
176
Cov.:
29
AF XY:
0.00226
AC XY:
1634
AN XY:
724360
show subpopulations
Gnomad4 AFR exome
AF:
0.0955
AC:
3180
AN:
33302
Gnomad4 AMR exome
AF:
0.00407
AC:
182
AN:
44702
Gnomad4 ASJ exome
AF:
0.00
AC:
0
AN:
26096
Gnomad4 EAS exome
AF:
0.00
AC:
0
AN:
39590
Gnomad4 SAS exome
AF:
0.000314
AC:
27
AN:
86090
Gnomad4 FIN exome
AF:
0.00
AC:
0
AN:
53394
Gnomad4 NFE exome
AF:
0.000139
AC:
154
AN:
1106276
Gnomad4 Remaining exome
AF:
0.00612
AC:
368
AN:
60150
Heterozygous variant carriers
0
155
310
464
619
774
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
102
204
306
408
510
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0258
AC:
3932
AN:
152258
Hom.:
164
Cov.:
32
AF XY:
0.0249
AC XY:
1855
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.0904
AC:
0.0904015
AN:
0.0904015
Gnomad4 AMR
AF:
0.00791
AC:
0.00791056
AN:
0.00791056
Gnomad4 ASJ
AF:
0.00
AC:
0
AN:
0
Gnomad4 EAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 SAS
AF:
0.000207
AC:
0.000207383
AN:
0.000207383
Gnomad4 FIN
AF:
0.00
AC:
0
AN:
0
Gnomad4 NFE
AF:
0.000309
AC:
0.000308705
AN:
0.000308705
Gnomad4 OTH
AF:
0.0151
AC:
0.0151372
AN:
0.0151372
Heterozygous variant carriers
0
177
353
530
706
883
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
36
72
108
144
180
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00953
Hom.:
173
Bravo
AF:
0.0293
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.0887
AC:
391
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.00825
AC:
1001
Asia WGS
AF:
0.00491
AC:
17
AN:
3478
EpiCase
AF:
0.0000546
EpiControl
AF:
0.000357

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Dec 28, 2017
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.073
BayesDel_addAF
Benign
-0.73
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
6.2
DANN
Benign
0.50
DEOGEN2
Benign
0.0079
T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.069
N
LIST_S2
Benign
0.42
T;T
MetaRNN
Benign
0.0024
T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.20
N;.
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-1.8
N;N
REVEL
Benign
0.0080
Sift
Benign
0.17
T;T
Sift4G
Benign
0.36
T;T
Polyphen
0.0040
B;.
Vest4
0.19
MVP
0.15
MPC
0.062
ClinPred
0.0035
T
GERP RS
-0.31
Varity_R
0.089
gMVP
0.72
Mutation Taster
=90/10
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000013
dbscSNV1_RF
Benign
0.0020
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: rs7007084; hg19: chr8-24251659; API