15-58599318-T-TA

Position:

• chr15-58599318-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001110.4(ADAM10):​c.2152+279_2152+280insT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0682 in 141,624 control chromosomes in the GnomAD database, including 355 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.068 (355 hom., cov: 29)
• Consequence: ADAM10 NM_001110.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.29

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 15-58599318-T-TA is Benign according to our data. Variant chr15-58599318-T-TA is described in ClinVar as [Benign]. Clinvar id is 1245260.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM10	NM_001110.4	c.2152+279_2152+280insT		intron_variant		ENST00000260408.8
ADAM10	NM_001320570.2	c.2059+279_2059+280insT		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM10	ENST00000260408.8	c.2152+279_2152+280insT		intron_variant		1	NM_001110.4	P1

Frequencies

GnomAD3 genomes AF: 0.0681 AC: 9640 AN: 141560 Hom.: 353 Cov.: 29

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0530

Gnomad AMR AF: 0.0371

Gnomad ASJ AF: 0.0532

Gnomad EAS AF: 0.00546

Gnomad SAS AF: 0.0346

Gnomad FIN AF: 0.0772

Gnomad MID AF: 0.0408

Gnomad NFE AF: 0.0607

Gnomad OTH AF: 0.0601

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0682 AC: 9654 AN: 141624 Hom.: 355 Cov.: 29 AF XY: 0.0678 AC XY: 4647 AN XY: 68578

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0370

Gnomad4 ASJ AF: 0.0532

Gnomad4 EAS AF: 0.00547

Gnomad4 SAS AF: 0.0347

Gnomad4 FIN AF: 0.0772

Gnomad4 NFE AF: 0.0607

Gnomad4 OTH AF: 0.0596

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs376724177; hg19: chr15-58891517;