chr8-24398522-G-C

Variant names:

• chr8-24398522-G-C
• rs200386440
• NM_014479.3:c.733G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014479.3(ADAMDEC1):​c.733G>C​(p.Val245Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 1,601,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V245M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ADAMDEC1 NM_014479.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22805917).

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.733G>C	p.Val245Leu	missense	Exon 8 of 14	NP_055294.1	O15204-1
	ADAMDEC1	NM_001145271.2		c.496G>C	p.Val166Leu	missense	Exon 9 of 15	NP_001138743.1	O15204-2
	ADAMDEC1	NM_001145272.2		c.496G>C	p.Val166Leu	missense	Exon 7 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.733G>C	p.Val245Leu	missense	Exon 8 of 14	ENSP00000256412.4	O15204-1
	ADAMDEC1	ENST00000522298.1	TSL:2	c.496G>C	p.Val166Leu	missense	Exon 7 of 13	ENSP00000428993.1	O15204-2
	ADAMDEC1	ENST00000893450.1		c.691-352G>C		intron	N/A	ENSP00000563509.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152032 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449654 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 721958

African (AFR) AF: 0.0000302 AC: 1 AN: 33070

American (AMR) AF: 0.00 AC: 0 AN: 42574

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26000

East Asian (EAS) AF: 0.00 AC: 0 AN: 39490

South Asian (SAS) AF: 0.00 AC: 0 AN: 85538

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103952

Other (OTH) AF: 0.00 AC: 0 AN: 60000

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152032 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74240

African (AFR) AF: 0.0000242 AC: 1 AN: 41402

American (AMR) AF: 0.00 AC: 0 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	5.1
DANN	Benign	0.83
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	0.81	L
PhyloP100		-1.3
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.24
Sift	Benign	0.14	T
Sift4G	Benign	0.20	T
Polyphen		0.10	B
Vest4		0.16
MutPred		0.72		Loss of catalytic residue at V245 (P = 0.2988)
MVP		0.32
MPC		0.061
ClinPred		0.15	T
GERP RS		-11
Varity_R		0.12
gMVP		0.45
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200386440; hg19: chr8-24256035;