rs3765124

chr8-24404013-A-Gchr8-24404013-A-T

Variant summary

Our verdict is Benign. Variant got -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. 13/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMDEC1	NM_014479.3	c.1331A>G	p.Asn444Ser	missense_variant	13/14	ENST00000256412.8
ADAM7-AS1	NR_125808.1	n.80-16022T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMDEC1	ENST00000256412.8	c.1331A>G	p.Asn444Ser	missense_variant	13/14	1	NM_014479.3	P1
ADAM7-AS1	ENST00000519689.1	n.185-16022T>C		intron_variant, non_coding_transcript_variant		4

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

GnomAD3 exomes AF: 0.402 AC: 100789 AN: 250754 Hom.: 21616 AF XY: 0.408 AC XY: 55242 AN XY: 135514

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 SAS exome AF: 0.429

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

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.465

Gnomad4 ASJ exome AF: 0.504

Gnomad4 EAS exome AF: 0.225

Gnomad4 SAS exome AF: 0.427

Gnomad4 FIN exome AF: 0.424

Gnomad4 NFE exome AF: 0.436

Gnomad4 OTH exome AF: 0.404

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

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.407

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.352

Alfa AF: 0.408 Hom.: 22016

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 v4.3

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;T
MetaRNN	Benign	0.00031	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.1	L;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Benign	0.064
Sift	Benign	0.25	T;T
Sift4G	Uncertain	0.051	T;D
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

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

Publications

LitVar

Other links and lift over

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