8-24404013-A-G

Variant names:

• chr8-24404013-A-G
• rs3765124
• NM_014479.3:c.1331A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014479.3(ADAMDEC1):​c.1331A>G​(p.Asn444Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 1,611,798 control chromosomes in the GnomAD database, including 144,173 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (10343 hom., cov: 32)
  • Exomes 𝑓: 0.42 (133830 hom.)
• Consequence: ADAMDEC1 NM_014479.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.437
• Publications: 32 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.05593E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMDEC1	NM_014479.3	MANE Select	c.1331A>G	p.Asn444Ser	missense	Exon 13 of 14	NP_055294.1
	ADAMDEC1	NM_001145271.2		c.1094A>G	p.Asn365Ser	missense	Exon 14 of 15	NP_001138743.1
	ADAMDEC1	NM_001145272.2		c.1094A>G	p.Asn365Ser	missense	Exon 12 of 13	NP_001138744.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMDEC1	ENST00000256412.8	TSL:1 MANE Select	c.1331A>G	p.Asn444Ser	missense	Exon 13 of 14	ENSP00000256412.4
	ADAMDEC1	ENST00000522298.1	TSL:2	c.1094A>G	p.Asn365Ser	missense	Exon 12 of 13	ENSP00000428993.1
	ADAMDEC1	ENST00000520193.1	TSL:2	n.*1295A>G		non_coding_transcript_exon	Exon 14 of 15	ENSP00000431008.1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52117 AN: 151806 Hom.: 10348 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.357

GnomAD2 exomes AF: 0.402 AC: 100789 AN: 250754 AF XY: 0.408

Gnomad AFR exome AF: 0.136

Gnomad AMR exome AF: 0.468

Gnomad ASJ exome AF: 0.506

Gnomad EAS exome AF: 0.191

Gnomad FIN exome AF: 0.426

Gnomad NFE exome AF: 0.432

Gnomad OTH exome AF: 0.425

GnomAD4 exome AF: 0.423 AC: 616932 AN: 1459874 Hom.: 133830 Cov.: 35 AF XY: 0.424 AC XY: 308249 AN XY: 726278

African (AFR) AF: 0.132 AC: 4418 AN: 33458

American (AMR) AF: 0.465 AC: 20780 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 13162 AN: 26110

East Asian (EAS) AF: 0.225 AC: 8902 AN: 39616

South Asian (SAS) AF: 0.427 AC: 36798 AN: 86174

European-Finnish (FIN) AF: 0.424 AC: 22649 AN: 53400

Middle Eastern (MID) AF: 0.385 AC: 2218 AN: 5756

European-Non Finnish (NFE) AF: 0.436 AC: 483630 AN: 1110400

Other (OTH) AF: 0.404 AC: 24375 AN: 60318

GnomAD4 genome AF: 0.343 AC: 52109 AN: 151924 Hom.: 10343 Cov.: 32 AF XY: 0.344 AC XY: 25567 AN XY: 74224

African (AFR) AF: 0.143 AC: 5947 AN: 41478

American (AMR) AF: 0.427 AC: 6511 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1719 AN: 3472

East Asian (EAS) AF: 0.187 AC: 968 AN: 5164

South Asian (SAS) AF: 0.407 AC: 1952 AN: 4800

European-Finnish (FIN) AF: 0.421 AC: 4443 AN: 10544

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29415 AN: 67924

Other (OTH) AF: 0.352 AC: 743 AN: 2108

Alfa AF: 0.397 Hom.: 42803

Bravo AF: 0.332

TwinsUK AF: 0.440 AC: 1632

ALSPAC AF: 0.426 AC: 1641

ESP6500AA AF: 0.154 AC: 677

ESP6500EA AF: 0.442 AC: 3804

ExAC AF: 0.394 AC: 47775

Asia WGS AF: 0.312 AC: 1085 AN: 3476

EpiCase AF: 0.421

EpiControl AF: 0.433

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.61
DEOGEN2	Benign	0.065	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.31	T
MetaRNN	Benign	0.00031	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.44
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.064
Sift	Benign	0.25	T
Sift4G	Uncertain	0.051	T
Polyphen		0.93	P
Vest4		0.053
MPC		0.058
ClinPred		0.065	T
GERP RS		0.41
Varity_R		0.049
gMVP		0.46
Mutation Taster		=99/1	polymorphism (auto)

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: rs3765124; hg19: chr8-24261526; COSMIC: COSV56475392; COSMIC: COSV56475392;