8-24384536-T-C

Variant names:

• chr8-24384536-T-C
• rs1441794912
• NM_014479.3:c.32T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014479.3(ADAMDEC1):​c.32T>C​(p.Val11Ala) 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 benign outcome for this variant. 16/22 in silico tools predict a benign 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.157
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.066685945).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMDEC1	NM_014479.3	MANE Select	c.32T>C	p.Val11Ala	missense	Exon 1 of 14	NP_055294.1	O15204-1
	ADAMDEC1	NM_001145271.2		c.-296T>C		5_prime_UTR	Exon 1 of 15	NP_001138743.1	O15204-2
	ADAMDEC1	NM_001145272.2		c.-87T>C		5_prime_UTR	Exon 1 of 13	NP_001138744.1	O15204-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMDEC1	ENST00000256412.8	TSL:1 MANE Select	c.32T>C	p.Val11Ala	missense	Exon 1 of 14	ENSP00000256412.4	O15204-1
	ADAMDEC1	ENST00000893450.1		c.32T>C	p.Val11Ala	missense	Exon 1 of 13	ENSP00000563509.1
	ADAMDEC1	ENST00000522298.1	TSL:2	c.-87T>C		5_prime_UTR	Exon 1 of 13	ENSP00000428993.1	O15204-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.1
DANN	Benign	0.87
DEOGEN2	Benign	0.0076	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.16
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.047
Sift	Benign	0.31	T
Sift4G	Benign	0.37	T
Polyphen		0.14	B
Vest4		0.14
MutPred		0.53		Gain of helix (P = 0.0325)
MVP		0.076
MPC		0.063
ClinPred		0.23	T
GERP RS		-3.3
PromoterAI		0.029	Neutral
Varity_R		0.024
gMVP		0.44
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs1441794912; hg19: chr8-24242049;