NM_014479.3:c.131T>G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_014479.3(ADAMDEC1):​c.131T>G​(p.Ile44Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,611,326 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I44T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0055 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00058 (5 hom.)
• Consequence: ADAMDEC1 NM_014479.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.55
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012194008).
• BP6: Variant 8-24392304-T-G is Benign according to our data. Variant chr8-24392304-T-G is described in ClinVar as Benign. ClinVar VariationId is 717905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00547 (833/152264) while in subpopulation AFR AF = 0.0178 (740/41568). AF 95% confidence interval is 0.0167. There are 6 homozygotes in GnomAd4. There are 398 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

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>G	p.Ile44Arg	missense	Exon 2 of 14	NP_055294.1	O15204-1
	ADAMDEC1	NM_001145271.2		c.-107T>G		5_prime_UTR	Exon 3 of 15	NP_001138743.1	O15204-2
	ADAMDEC1	NM_001145272.2		c.-30-958T>G		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>G	p.Ile44Arg	missense	Exon 2 of 14	ENSP00000256412.4	O15204-1
	ADAMDEC1	ENST00000893450.1		c.131T>G	p.Ile44Arg	missense	Exon 2 of 13	ENSP00000563509.1
	ADAMDEC1	ENST00000522298.1	TSL:2	c.-30-958T>G		intron	N/A	ENSP00000428993.1	O15204-2

Frequencies

GnomAD3 genomes AF: 0.00546 AC: 831 AN: 152146 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00452

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00147 AC: 365 AN: 248334 AF XY: 0.00117

Gnomad AFR exome AF: 0.0192

Gnomad AMR exome AF: 0.00123

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000797

Gnomad OTH exome AF: 0.000667

GnomAD4 exome AF: 0.000579 AC: 845 AN: 1459062 Hom.: 5 Cov.: 30 AF XY: 0.000491 AC XY: 356 AN XY: 725738

African (AFR) AF: 0.0189 AC: 630 AN: 33370

American (AMR) AF: 0.00147 AC: 65 AN: 44366

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26082

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

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85596

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

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5758

European-Non Finnish (NFE) AF: 0.0000720 AC: 80 AN: 1110664

Other (OTH) AF: 0.00108 AC: 65 AN: 60292

GnomAD4 genome AF: 0.00547 AC: 833 AN: 152264 Hom.: 6 Cov.: 32 AF XY: 0.00535 AC XY: 398 AN XY: 74436

African (AFR) AF: 0.0178 AC: 740 AN: 41568

American (AMR) AF: 0.00452 AC: 69 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68020

Other (OTH) AF: 0.00568 AC: 12 AN: 2112

Alfa AF: 0.00206 Hom.: 5

Bravo AF: 0.00631

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0186 AC: 82

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00184 AC: 223

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.037	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.6
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.98	D
Vest4		0.39
MVP		0.63
MPC		0.098
ClinPred		0.077	T
GERP RS		5.3
Varity_R		0.81
gMVP		0.90
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;