15-83704176-G-A

Variant names:

• chr15-83704176-G-A
• rs11639223
• NM_207517.3:c.70-213G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_207517.3(ADAMTSL3):​c.70-213G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,150 control chromosomes in the GnomAD database, including 1,564 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1564 hom., cov: 32)
• Consequence: ADAMTSL3 NM_207517.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.13
• Publications: 2 publications found

Genes affected

ADAMTSL3 (HGNC:14633): (ADAMTS like 3) Predicted to be involved in extracellular matrix organization. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 15-83704176-G-A is Benign according to our data. Variant chr15-83704176-G-A is described in ClinVar as [Benign]. Clinvar id is 1247467.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL3	NM_207517.3	c.70-213G>A		intron_variant	Intron 2 of 29	ENST00000286744.10	NP_997400.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL3	ENST00000286744.10	c.70-213G>A		intron_variant	Intron 2 of 29	1	NM_207517.3	ENSP00000286744.5

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19203 AN: 152032 Hom.: 1568 Cov.: 32

Gnomad AFR AF: 0.0329

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.0966

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0210

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.126 AC: 19191 AN: 152150 Hom.: 1564 Cov.: 32 AF XY: 0.130 AC XY: 9653 AN XY: 74370

African (AFR) AF: 0.0328 AC: 1363 AN: 41534

American (AMR) AF: 0.0964 AC: 1474 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 515 AN: 3470

East Asian (EAS) AF: 0.0209 AC: 108 AN: 5170

South Asian (SAS) AF: 0.265 AC: 1274 AN: 4814

European-Finnish (FIN) AF: 0.181 AC: 1913 AN: 10580

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11947 AN: 67986

Other (OTH) AF: 0.119 AC: 250 AN: 2104

Alfa AF: 0.164 Hom.: 1254

Bravo AF: 0.111

Asia WGS AF: 0.120 AC: 419 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0020
DANN	Benign	0.45
PhyloP100		-4.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs11639223; hg19: chr15-84372928;