rs35372591

Variant names:

• chr8-24392304-T-C
• rs35372591
• NM_014479.3:c.131T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-24392304-T-C
• chr8-24392304-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014479.3(ADAMDEC1):​c.131T>C​(p.Ile44Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,070 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I44R) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ADAMDEC1 NM_014479.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.55
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.131T>C	p.Ile44Thr	missense	Exon 2 of 14	NP_055294.1	O15204-1
	ADAMDEC1	NM_001145271.2		c.-107T>C		5_prime_UTR	Exon 3 of 15	NP_001138743.1	O15204-2
	ADAMDEC1	NM_001145272.2		c.-30-958T>C		intron	N/A	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.131T>C	p.Ile44Thr	missense	Exon 2 of 14	ENSP00000256412.4	O15204-1
	ADAMDEC1	ENST00000893450.1		c.131T>C	p.Ile44Thr	missense	Exon 2 of 13	ENSP00000563509.1
	ADAMDEC1	ENST00000522298.1	TSL:2	c.-30-958T>C		intron	N/A	ENSP00000428993.1	O15204-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459070 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725742

African (AFR) AF: 0.00 AC: 0 AN: 33372

American (AMR) AF: 0.00 AC: 0 AN: 44368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39552

South Asian (SAS) AF: 0.00 AC: 0 AN: 85598

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110664

Other (OTH) AF: 0.00 AC: 0 AN: 60294

GnomAD4 genome Cov.: 32

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	0.073
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.025	T
Eigen	Benign	0.012
Eigen_PC	Benign	0.065
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.6
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.14
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.36	B
Vest4		0.41
MutPred		0.81		Loss of stability (P = 0.0352)
MVP		0.43
MPC		0.14
ClinPred		0.85	D
GERP RS		5.3
Varity_R		0.38
gMVP		0.74
Mutation Taster		=88/12	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: rs35372591; hg19: chr8-24249817;