rs779812850

Variant names:

• chr8-24394070-C-A
• rs779812850
• NM_014479.3:c.286C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-24394070-C-A
• chr8-24394070-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014479.3(ADAMDEC1):​c.286C>A​(p.His96Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,611,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: ADAMDEC1 NM_014479.3 missense, splice_region
• Scores: Splicing: ADA: 0.00001278
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.767
• Publications: 1 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06138271).

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.286C>A	p.His96Asn	missense splice_region	Exon 4 of 14	NP_055294.1	O15204-1
	ADAMDEC1	NM_001145271.2		c.49C>A	p.His17Asn	missense splice_region	Exon 5 of 15	NP_001138743.1	O15204-2
	ADAMDEC1	NM_001145272.2		c.49C>A	p.His17Asn	missense splice_region	Exon 3 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.286C>A	p.His96Asn	missense splice_region	Exon 4 of 14	ENSP00000256412.4	O15204-1
	ADAMDEC1	ENST00000893450.1		c.286C>A	p.His96Asn	missense splice_region	Exon 4 of 13	ENSP00000563509.1
	ADAMDEC1	ENST00000522298.1	TSL:2	c.49C>A	p.His17Asn	missense splice_region	Exon 3 of 13	ENSP00000428993.1	O15204-2

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152138 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000958 AC: 24 AN: 250596 AF XY: 0.0000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000609

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1459096 Hom.: 0 Cov.: 29 AF XY: 0.0000179 AC XY: 13 AN XY: 726064

African (AFR) AF: 0.00 AC: 0 AN: 33398

American (AMR) AF: 0.000493 AC: 22 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39594

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

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

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1109722

Other (OTH) AF: 0.0000166 AC: 1 AN: 60294

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152138 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74320

African (AFR) AF: 0.00 AC: 0 AN: 41434

American (AMR) AF: 0.000196 AC: 3 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions as Germline

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	0.060
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.82
DANN	Benign	0.70
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.47	N
PhyloP100		-0.77
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.33	N
REVEL	Benign	0.061
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.012	B
Vest4		0.16
MutPred		0.49		Loss of catalytic residue at L98 (P = 0.0568)
MVP		0.20
MPC		0.059
ClinPred		0.020	T
GERP RS		-1.4
Varity_R		0.076
gMVP		0.49
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000013
dbscSNV1_RF	Benign	0.0060
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: rs779812850; hg19: chr8-24251583;