10-133263224-C-G

Variant names:

• chr10-133263224-C-G
• rs774027930
• NM_001109.5:c.2407G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001109.5(ADAM8):​c.2407G>C​(p.Gly803Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,608,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 35)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: ADAM8 NM_001109.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.176
• Publications: 0 publications found

Genes affected

ADAM8 (HGNC:215): (ADAM metallopeptidase domain 8) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The protein encoded by this gene may be involved in cell adhesion during neurodegeneration, and it is thought to be a target for allergic respiratory diseases, including asthma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13670173).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001109.5. 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
	ADAM8	NM_001109.5	MANE Select	c.2407G>C	p.Gly803Arg	missense	Exon 23 of 23	NP_001100.3	P78325-1
	ADAM8	NM_001164490.2		c.2134G>C	p.Gly712Arg	missense	Exon 20 of 20	NP_001157962.1	P78325-2
	ADAM8	NM_001164489.2		c.*11G>C		3_prime_UTR	Exon 22 of 22	NP_001157961.1	P78325-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM8	ENST00000445355.8	TSL:1 MANE Select	c.2407G>C	p.Gly803Arg	missense	Exon 23 of 23	ENSP00000453302.1	P78325-1
	ADAM8	ENST00000415217.7	TSL:1	c.*11G>C		3_prime_UTR	Exon 22 of 22	ENSP00000453855.1	P78325-3
	ADAM8	ENST00000897047.1		c.2401G>C	p.Gly801Arg	missense	Exon 23 of 23	ENSP00000567106.1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152222 Hom.: 0 Cov.: 35

Gnomad AFR AF: 0.0000482

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: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000734 AC: 18 AN: 245294 AF XY: 0.0000752

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000163

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000116 AC: 169 AN: 1456164 Hom.: 0 Cov.: 32 AF XY: 0.000116 AC XY: 84 AN XY: 723800

African (AFR) AF: 0.0000301 AC: 1 AN: 33270

American (AMR) AF: 0.00 AC: 0 AN: 44002

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25896

East Asian (EAS) AF: 0.00 AC: 0 AN: 39566

South Asian (SAS) AF: 0.00 AC: 0 AN: 85800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.000148 AC: 164 AN: 1108456

Other (OTH) AF: 0.0000665 AC: 4 AN: 60170

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152222 Hom.: 0 Cov.: 35 AF XY: 0.0000672 AC XY: 5 AN XY: 74366

African (AFR) AF: 0.0000482 AC: 2 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15280

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000141 Hom.: 0

Bravo AF: 0.0000680

ExAC AF: 0.0000824 AC: 10

ClinVar

ClinVar submissions

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	0.14
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.098	T
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.14	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.18
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.8	N
Sift	Benign	0.079	T
Sift4G	Benign	0.36	T
Polyphen		0.94	P
Vest4		0.17
MVP		0.57
MPC		0.60
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.045
gMVP		0.079
Mutation Taster		=95/5	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: rs774027930; hg19: chr10-135076728;