rs61733287

Variant names:

• chr10-133263747-C-A
• NM_001109.5:c.2338G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-133263747-C-A
• chr10-133263747-C-G
• chr10-133263747-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001109.5(ADAM8):​c.2338G>T​(p.Ala780Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,417,416 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. 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. A780T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 36)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ADAM8 NM_001109.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.520

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.096250474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM8	NM_001109.5	c.2338G>T	p.Ala780Ser	missense_variant	Exon 22 of 23	ENST00000445355.8	NP_001100.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM8	ENST00000445355.8	c.2338G>T	p.Ala780Ser	missense_variant	Exon 22 of 23	1	NM_001109.5	ENSP00000453302.1
ADAM8	ENST00000415217.7	c.2171G>T	p.Arg724Leu	missense_variant	Exon 21 of 22	1		ENSP00000453855.1
ADAM8	ENST00000485491.6	c.2125-514G>T		intron_variant	Intron 19 of 19	2		ENSP00000453043.1
ADAM8	ENST00000559018.1	n.119G>T		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1417416 Hom.: 0 Cov.: 37 AF XY: 0.00000142 AC XY: 1 AN XY: 702160

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.18e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.56
DANN	Benign	0.68
DEOGEN2	Benign	0.080	T
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.096	T
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.58	N
Sift	Benign	0.35	T
Sift4G	Benign	0.69	T
Polyphen		0.66	P
Vest4		0.15
MVP		0.47
MPC		0.26
GERP RS		-0.75
Varity_R		0.044
gMVP		0.075

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-135077251;