15-58599899-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001110.4(ADAM10):c.2026-175A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0346 in 151,968 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.035 (108 hom., cov: 32)
• Consequence: ADAM10 NM_001110.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.45

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 15-58599899-T-A is Benign according to our data. Variant chr15-58599899-T-A is described in ClinVar as [Benign]. Clinvar id is 1240622.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM10	NM_001110.4	c.2026-175A>T		intron_variant		ENST00000260408.8
ADAM10	NM_001320570.2	c.1933-175A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM10	ENST00000260408.8	c.2026-175A>T		intron_variant		1	NM_001110.4	P1

Frequencies

GnomAD3 genomes AF: 0.0345 AC: 5244 AN: 151850 Hom.: 106 Cov.: 32

Gnomad AFR AF: 0.0646

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0238

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0240

Gnomad FIN AF: 0.0171

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0260

Gnomad OTH AF: 0.0312

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

GnomAD4 genome AF: 0.0346 AC: 5256 AN: 151968 Hom.: 108 Cov.: 32 AF XY: 0.0339 AC XY: 2521 AN XY: 74298

Gnomad4 AFR AF: 0.0647

Gnomad4 AMR AF: 0.0238

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0238

Gnomad4 FIN AF: 0.0171

Gnomad4 NFE AF: 0.0260

Gnomad4 OTH AF: 0.0309

Alfa AF: 0.0163 Hom.: 7

Bravo AF: 0.0346

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.43
Dann	Benign	0.63

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: rs75112899; hg19: chr15-58892098;