NM_014479.3:c.242T>C

Variant names:

• chr8-24393296-T-C
• rs77012108
• NM_014479.3:c.242T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014479.3(ADAMDEC1):​c.242T>C​(p.Ile81Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00436 in 1,605,972 control chromosomes in the GnomAD database, including 279 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (135 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (144 hom.)
• Consequence: ADAMDEC1 NM_014479.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.04
• Publications: 5 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=0.0026058555).
• BP6: Variant 8-24393296-T-C is Benign according to our data. Variant chr8-24393296-T-C is described in ClinVar as Benign. ClinVar VariationId is 781120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0809 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMDEC1	NM_014479.3	MANE Select	c.242T>C	p.Ile81Thr	missense	Exon 3 of 14	NP_055294.1	O15204-1
	ADAMDEC1	NM_001145271.2		c.5T>C	p.Ile2Thr	missense	Exon 4 of 15	NP_001138743.1	O15204-2
	ADAMDEC1	NM_001145272.2		c.5T>C	p.Ile2Thr	missense	Exon 2 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.242T>C	p.Ile81Thr	missense	Exon 3 of 14	ENSP00000256412.4	O15204-1
	ADAMDEC1	ENST00000893450.1		c.242T>C	p.Ile81Thr	missense	Exon 3 of 13	ENSP00000563509.1
	ADAMDEC1	ENST00000522298.1	TSL:2	c.5T>C	p.Ile2Thr	missense	Exon 2 of 13	ENSP00000428993.1	O15204-2

Frequencies

GnomAD3 genomes AF: 0.0236 AC: 3588 AN: 152088 Hom.: 134 Cov.: 32

Gnomad AFR AF: 0.0830

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00721

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00597 AC: 1475 AN: 247076 AF XY: 0.00433

Gnomad AFR exome AF: 0.0836

Gnomad AMR exome AF: 0.00276

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000133

Gnomad OTH exome AF: 0.00368

GnomAD4 exome AF: 0.00234 AC: 3399 AN: 1453766 Hom.: 144 Cov.: 28 AF XY: 0.00195 AC XY: 1410 AN XY: 723270

African (AFR) AF: 0.0852 AC: 2820 AN: 33098

American (AMR) AF: 0.00366 AC: 161 AN: 43998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25988

East Asian (EAS) AF: 0.00 AC: 0 AN: 39360

South Asian (SAS) AF: 0.000236 AC: 20 AN: 84900

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53300

Middle Eastern (MID) AF: 0.00228 AC: 13 AN: 5698

European-Non Finnish (NFE) AF: 0.0000433 AC: 48 AN: 1107306

Other (OTH) AF: 0.00561 AC: 337 AN: 60118

GnomAD4 genome AF: 0.0237 AC: 3605 AN: 152206 Hom.: 135 Cov.: 32 AF XY: 0.0228 AC XY: 1698 AN XY: 74432

African (AFR) AF: 0.0832 AC: 3455 AN: 41522

American (AMR) AF: 0.00720 AC: 110 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68008

Other (OTH) AF: 0.0133 AC: 28 AN: 2108

Alfa AF: 0.00934 Hom.: 110

Bravo AF: 0.0269

ESP6500AA AF: 0.0808 AC: 356

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00744 AC: 903

Asia WGS AF: 0.00463 AC: 16 AN: 3470

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	0.077
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.011
DANN	Benign	0.60
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0079	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.69	N
PhyloP100		-3.0
PrimateAI	Benign	0.37	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.030
Sift	Benign	0.81	T
Sift4G	Benign	0.83	T
Polyphen		0.0010	B
Vest4		0.18
MVP		0.040
MPC		0.066
ClinPred		0.0042	T
GERP RS		-11
Varity_R		0.030
gMVP		0.41
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs77012108; hg19: chr8-24250809;