15-58749813-T-G

Variant names:

• chr15-58749813-T-G
• rs653765
• NM_001110.4:c.-279A>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001110.4(ADAM10):​c.-279A>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000114 in 1,048,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: ADAM10 NM_001110.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.824
• Publications: 39 publications found

Genes affected

ADAM10 (HGNC:188): (ADAM metallopeptidase domain 10) Members of the ADAM family are cell surface proteins with a unique structure possessing both potential adhesion and protease domains. This gene encodes and ADAM family member that cleaves many proteins including TNF-alpha and E-cadherin. Alternate splicing results in multiple transcript variants encoding different proteins that may undergo similar processing. [provided by RefSeq, Feb 2016]

ADAM10 Gene-Disease associations (from GenCC):

• reticulate acropigmentation of Kitamura

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000286897 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS2: High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM10	NM_001110.4	c.-279A>C		upstream_gene_variant		ENST00000260408.8	NP_001101.1
ADAM10	NM_001320570.2	c.-279A>C		upstream_gene_variant			NP_001307499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM10	ENST00000260408.8	c.-279A>C		upstream_gene_variant		1	NM_001110.4	ENSP00000260408.3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.0000114 AC: 12 AN: 1048642 Hom.: 0 Cov.: 16 AF XY: 0.0000199 AC XY: 10 AN XY: 502078

African (AFR) AF: 0.00 AC: 0 AN: 21984

American (AMR) AF: 0.00 AC: 0 AN: 9662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14542

East Asian (EAS) AF: 0.00 AC: 0 AN: 26576

South Asian (SAS) AF: 0.000381 AC: 11 AN: 28840

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2876

European-Non Finnish (NFE) AF: 0.00000114 AC: 1 AN: 878850

Other (OTH) AF: 0.00 AC: 0 AN: 42960

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	15
DANN	Benign	0.64
PhyloP100		0.82
PromoterAI		0.047	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs653765; hg19: chr15-59042012;