Genetic Variant NM_014479.3:c.512C>T (chr8-24397341-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_014479.3(ADAMDEC1):c.512C>T(p.Ala171Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A171D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ADAMDEC1
NM_014479.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.497

Publications

0 publications found

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]

ADAMDEC1 links:

ADAM7-AS1 (HGNC:56152): (ADAM7, ADAMDEC1 and ADAM28 antisense RNA 1)

ADAM7-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39393723).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014479.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAMDEC1	NM_014479.3	MANE Select	c.512C>T	p.Ala171Val	missense	Exon 6 of 14	NP_055294.1	O15204-1
ADAMDEC1	NM_001145271.2		c.275C>T	p.Ala92Val	missense	Exon 7 of 15	NP_001138743.1	O15204-2
ADAMDEC1	NM_001145272.2		c.275C>T	p.Ala92Val	missense	Exon 5 of 13	NP_001138744.1	O15204-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAMDEC1	ENST00000256412.8	TSL:1 MANE Select	c.512C>T	p.Ala171Val	missense	Exon 6 of 14	ENSP00000256412.4	O15204-1
ADAMDEC1	ENST00000893450.1		c.512C>T	p.Ala171Val	missense	Exon 6 of 13	ENSP00000563509.1
ADAMDEC1	ENST00000522298.1	TSL:2	c.275C>T	p.Ala92Val	missense	Exon 5 of 13	ENSP00000428993.1	O15204-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461712

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727144

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111904

Other (OTH)

AF:

0.00

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.028

Eigen

Benign

0.032

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.53

M_CAP

Benign

0.0069

MetaRNN

Benign

0.39

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

PhyloP100

0.50

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.042

Sift

Benign

0.064

Sift4G

Benign

0.072

Polyphen

0.97

Vest4

0.34

MutPred

0.50

Loss of sheet (P = 0.0817)

MVP

0.40

MPC

0.087

ClinPred

0.84

GERP RS

2.8

Varity_R

0.16

gMVP

0.59

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over