15-83819661-CAAAAAAA-CAAAAAAAAAAA

Variant names:

• chr15-83819661-C-CAAAA
• rs11301352
• NM_207517.3:c.364-135_364-132dupAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_207517.3(ADAMTSL3):​c.364-135_364-132dupAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 403,506 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000025 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADAMTSL3 NM_207517.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.436
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207517.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL3	NM_207517.3	MANE Select	c.364-135_364-132dupAAAA		intron	N/A	NP_997400.2	P82987-1
	ADAMTSL3	NM_001301110.2		c.364-135_364-132dupAAAA		intron	N/A	NP_001288039.1	P82987-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL3	ENST00000286744.10	TSL:1 MANE Select	c.364-150_364-149insAAAA		intron	N/A	ENSP00000286744.5	P82987-1
	ADAMTSL3	ENST00000567476.1	TSL:1	c.364-150_364-149insAAAA		intron	N/A	ENSP00000456313.1	P82987-2
	ADAMTSL3	ENST00000963409.1		c.364-150_364-149insAAAA		intron	N/A	ENSP00000633468.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 120482 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000248 AC: 1 AN: 403506 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 211450

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 11420

American (AMR) AF: 0.00 AC: 0 AN: 17478

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12352

East Asian (EAS) AF: 0.00 AC: 0 AN: 28808

South Asian (SAS) AF: 0.00 AC: 0 AN: 37496

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27500

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1776

European-Non Finnish (NFE) AF: 0.00000411 AC: 1 AN: 243282

Other (OTH) AF: 0.00 AC: 0 AN: 23394

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 120482 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 57152

African (AFR) AF: 0.00 AC: 0 AN: 32054

American (AMR) AF: 0.00 AC: 0 AN: 12158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2962

East Asian (EAS) AF: 0.00 AC: 0 AN: 4248

South Asian (SAS) AF: 0.00 AC: 0 AN: 3552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5908

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 260

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 56922

Other (OTH) AF: 0.00 AC: 0 AN: 1638

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.44

Splicing

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

Other links and lift over

dbSNP: rs11301352; hg19: chr15-84488413;