10-133267938-C-T

Variant names:

• chr10-133267938-C-T
• rs1483847365
• ENST00000415217.7:c.2077G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001164489.2(ADAM8):​c.2077G>A​(p.Ala693Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000294 in 1,259,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: ADAM8 NM_001164489.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -7.49
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.055107057).
• BP6: Variant 10-133267938-C-T is Benign according to our data. Variant chr10-133267938-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3488544.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164489.2. 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.2244G>A	p.Pro748Pro	synonymous	Exon 20 of 23	NP_001100.3	P78325-1
	ADAM8	NM_001164489.2		c.2077G>A	p.Ala693Thr	missense	Exon 19 of 22	NP_001157961.1	P78325-3
	ADAM8	NM_001164490.2		c.2049G>A	p.Pro683Pro	synonymous	Exon 18 of 20	NP_001157962.1	P78325-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM8	ENST00000415217.7	TSL:1	c.2077G>A	p.Ala693Thr	missense	Exon 19 of 22	ENSP00000453855.1	P78325-3
	ADAM8	ENST00000445355.8	TSL:1 MANE Select	c.2244G>A	p.Pro748Pro	synonymous	Exon 20 of 23	ENSP00000453302.1	P78325-1
	ADAM8	ENST00000897047.1		c.2238G>A	p.Pro746Pro	synonymous	Exon 20 of 23	ENSP00000567106.1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152190 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000773

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000280 AC: 31 AN: 1107652 Hom.: 0 Cov.: 32 AF XY: 0.0000172 AC XY: 9 AN XY: 524472

African (AFR) AF: 0.00 AC: 0 AN: 23382

American (AMR) AF: 0.00 AC: 0 AN: 11030

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14470

East Asian (EAS) AF: 0.000442 AC: 12 AN: 27174

South Asian (SAS) AF: 0.000471 AC: 10 AN: 21222

European-Finnish (FIN) AF: 0.0000288 AC: 1 AN: 34776

Middle Eastern (MID) AF: 0.000995 AC: 3 AN: 3016

European-Non Finnish (NFE) AF: 0.00000323 AC: 3 AN: 928272

Other (OTH) AF: 0.0000451 AC: 2 AN: 44310

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152306 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74466

African (AFR) AF: 0.0000241 AC: 1 AN: 41570

American (AMR) AF: 0.00 AC: 0 AN: 15310

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

East Asian (EAS) AF: 0.000775 AC: 4 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.073
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.32
DANN	Benign	0.95
FATHMM_MKL	Benign	0.00086	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.055	T
PhyloP100		-7.5
PROVEAN	Benign	0.050	N
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.13	T
Vest4		0.067
MVP		0.51
GERP RS		-7.7
Mutation Taster		=97/3	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: rs1483847365; hg19: chr10-135081442;