chr8-24397343-G-A

Variant names:

• chr8-24397343-G-A
• rs200134300
• NM_014479.3:c.514G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014479.3(ADAMDEC1):​c.514G>A​(p.Val172Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000991 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000096 (0 hom.)
• Consequence: ADAMDEC1 NM_014479.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06257838).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMDEC1	NM_014479.3	c.514G>A	p.Val172Ile	missense_variant	Exon 6 of 14	ENST00000256412.8	NP_055294.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMDEC1	ENST00000256412.8	c.514G>A	p.Val172Ile	missense_variant	Exon 6 of 14	1	NM_014479.3	ENSP00000256412.4

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152130 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000638 AC: 16 AN: 250830 Hom.: 0 AF XY: 0.0000811 AC XY: 11 AN XY: 135566

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000965 AC: 141 AN: 1461734 Hom.: 0 Cov.: 31 AF XY: 0.0000839 AC XY: 61 AN XY: 727172

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000120

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152248 Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7 AN XY: 74442

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000756

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000741 AC: 9

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.3
DANN	Benign	0.78
DEOGEN2	Benign	0.0055	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.40	T;T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.063	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.74	N;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.14	N;N
REVEL	Benign	0.071
Sift	Benign	0.78	T;T
Sift4G	Benign	0.52	T;T
Polyphen		0.69	P;.
Vest4		0.21
MVP		0.10
MPC		0.054
ClinPred		0.034	T
GERP RS		-6.1
Varity_R		0.053
gMVP		0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs200134300; hg19: chr8-24254856; COSMIC: COSV56477810;