ENST00000415217.7:c.2053C>T

Variant names:

• chr10-133267962-G-A
• rs369930002
• ENST00000415217.7:c.2053C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The ENST00000415217.7(ADAM8):​c.2053C>T​(p.Leu685Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000238 in 1,262,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: ADAM8 ENST00000415217.7 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.32
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.076412946).
• BP6: Variant 10-133267962-G-A is Benign according to our data. Variant chr10-133267962-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2510424.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000415217.7. 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.2220C>T	p.Ala740Ala	synonymous	Exon 20 of 23	NP_001100.3	P78325-1
	ADAM8	NM_001164489.2		c.2053C>T	p.Leu685Phe	missense	Exon 19 of 22	NP_001157961.1	P78325-3
	ADAM8	NM_001164490.2		c.2025C>T	p.Ala675Ala	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.2053C>T	p.Leu685Phe	missense	Exon 19 of 22	ENSP00000453855.1	P78325-3
	ADAM8	ENST00000445355.8	TSL:1 MANE Select	c.2220C>T	p.Ala740Ala	synonymous	Exon 20 of 23	ENSP00000453302.1	P78325-1
	ADAM8	ENST00000897047.1		c.2214C>T	p.Ala738Ala	synonymous	Exon 20 of 23	ENSP00000567106.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152234 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: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 29454 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000234 AC: 26 AN: 1109950 Hom.: 0 Cov.: 31 AF XY: 0.0000152 AC XY: 8 AN XY: 525832

African (AFR) AF: 0.00 AC: 0 AN: 23542

American (AMR) AF: 0.00 AC: 0 AN: 11042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14474

East Asian (EAS) AF: 0.00 AC: 0 AN: 27412

South Asian (SAS) AF: 0.000190 AC: 4 AN: 21020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35758

Middle Eastern (MID) AF: 0.000953 AC: 3 AN: 3148

European-Non Finnish (NFE) AF: 0.0000194 AC: 18 AN: 929206

Other (OTH) AF: 0.0000225 AC: 1 AN: 44348

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152234 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74366

African (AFR) AF: 0.0000241 AC: 1 AN: 41462

American (AMR) AF: 0.00 AC: 0 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68044

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

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.0000567

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000128 AC: 1

ExAC AF: 0.0000493 AC: 5

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	0.069
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.39
DANN	Uncertain	0.99
FATHMM_MKL	Benign	0.0069	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.00093	T
MetaRNN	Benign	0.076	T
PhyloP100		-2.3
PROVEAN	Benign	0.11	N
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.14	T
Vest4		0.062
MVP		0.52
GERP RS		-5.7
Mutation Taster		=99/1	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: rs369930002; hg19: chr10-135081466;