15-83819661-CAAAAAAA-CAAAAA

Variant names:

• chr15-83819661-CAA-C
• rs11301352
• NM_207517.3:c.364-133_364-132delAA

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BS1

The NM_207517.3(ADAMTSL3):​c.364-133_364-132delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 501,936 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0033 (1 hom., cov: 0)
  • Exomes 𝑓: 0.22 (0 hom.)
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Variant has high frequency in the EAS (0.27) population. However there is too low homozygotes in high coverage region: (expected more than 3446, got 1).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00331 (398/120360) while in subpopulation EAS AF = 0.0227 (96/4228). AF 95% confidence interval is 0.019. There are 1 homozygotes in GnomAd4. There are 212 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

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.364-133_364-132delAA		intron	N/A	NP_997400.2	P82987-1
	ADAMTSL3	NM_001301110.2		c.364-133_364-132delAA		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.364-149_364-148delAA		intron	N/A	ENSP00000286744.5	P82987-1
	ADAMTSL3	ENST00000567476.1	TSL:1	c.364-149_364-148delAA		intron	N/A	ENSP00000456313.1	P82987-2
	ADAMTSL3	ENST00000963409.1		c.364-149_364-148delAA		intron	N/A	ENSP00000633468.1

Frequencies

GnomAD3 genomes AF: 0.00331 AC: 399 AN: 120406 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00144

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00272

Gnomad ASJ AF: 0.00101

Gnomad EAS AF: 0.0226

Gnomad SAS AF: 0.00592

Gnomad FIN AF: 0.0108

Gnomad MID AF: 0.00769

Gnomad NFE AF: 0.00229

Gnomad OTH AF: 0.00244

GnomAD4 exome AF: 0.217 AC: 82788 AN: 381576 Hom.: 0 AF XY: 0.218 AC XY: 43582 AN XY: 200146

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

African (AFR) AF: 0.206 AC: 2178 AN: 10558

American (AMR) AF: 0.228 AC: 3761 AN: 16488

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 2440 AN: 11632

East Asian (EAS) AF: 0.275 AC: 7495 AN: 27244

South Asian (SAS) AF: 0.238 AC: 8672 AN: 36424

European-Finnish (FIN) AF: 0.201 AC: 5216 AN: 26014

Middle Eastern (MID) AF: 0.236 AC: 395 AN: 1676

European-Non Finnish (NFE) AF: 0.209 AC: 47927 AN: 229498

Other (OTH) AF: 0.213 AC: 4704 AN: 22042

⚠️ 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 AF: 0.00331 AC: 398 AN: 120360 Hom.: 1 Cov.: 0 AF XY: 0.00371 AC XY: 212 AN XY: 57100

African (AFR) AF: 0.00143 AC: 46 AN: 32070

American (AMR) AF: 0.00272 AC: 33 AN: 12152

Ashkenazi Jewish (ASJ) AF: 0.00101 AC: 3 AN: 2956

East Asian (EAS) AF: 0.0227 AC: 96 AN: 4228

South Asian (SAS) AF: 0.00568 AC: 20 AN: 3524

European-Finnish (FIN) AF: 0.0108 AC: 64 AN: 5902

Middle Eastern (MID) AF: 0.00862 AC: 2 AN: 232

European-Non Finnish (NFE) AF: 0.00229 AC: 130 AN: 56876

Other (OTH) AF: 0.00244 AC: 4 AN: 1640

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism

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: rs11301352; hg19: chr15-84488413;