9-18573362-G-A

Variant names:

• chr9-18573362-G-A
• rs13299349
• NM_001040272.6:c.238-668G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040272.6(ADAMTSL1):​c.238-668G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 154,628 control chromosomes in the GnomAD database, including 6,289 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (6159 hom., cov: 31)
  • Exomes 𝑓: 0.31 (130 hom.)
• Consequence: ADAMTSL1 NM_001040272.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370
• Publications: 17 publications found

Genes affected

ADAMTSL1 (HGNC:14632): (ADAMTS like 1) This gene encodes a secreted protein and member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) family. This protein lacks the metalloproteinase and disintegrin-like domains, which are typical of the ADAMTS family, but contains other ADAMTS domains, including the thrombospondin type 1 motif. This protein may have important functions in the extracellular matrix. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jul 2008]

MIR3152 (HGNC:38379): (microRNA 3152) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040272.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL1	NM_001040272.6	MANE Select	c.238-668G>A		intron	N/A	NP_001035362.3
	MIR3152	NR_036107.1		n.57G>A		non_coding_transcript_exon	Exon 1 of 1
	ADAMTSL1	NM_052866.5		c.238-668G>A		intron	N/A	NP_443098.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL1	ENST00000380548.9	TSL:5 MANE Select	c.238-668G>A		intron	N/A	ENSP00000369921.4
	ADAMTSL1	ENST00000327883.11	TSL:1	c.238-668G>A		intron	N/A	ENSP00000327887.7
	ADAMTSL1	ENST00000380566.8	TSL:1	c.238-668G>A		intron	N/A	ENSP00000369940.4

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41261 AN: 151800 Hom.: 6156 Cov.: 31

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.293

GnomAD2 exomes AF: 0.321 AC: 1927 AN: 6010 AF XY: 0.328

Gnomad AFR exome AF: 0.177

Gnomad AMR exome AF: 0.353

Gnomad ASJ exome AF: 0.417

Gnomad EAS exome AF: 0.125

Gnomad NFE exome AF: 0.329

Gnomad OTH exome AF: 0.362

GnomAD4 exome AF: 0.306 AC: 829 AN: 2710 Hom.: 130 Cov.: 0 AF XY: 0.303 AC XY: 421 AN XY: 1388

African (AFR) AF: 0.216 AC: 16 AN: 74

American (AMR) AF: 0.375 AC: 6 AN: 16

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 1 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.229 AC: 22 AN: 96

European-Finnish (FIN) AF: 0.305 AC: 130 AN: 426

Middle Eastern (MID) AF: 0.323 AC: 527 AN: 1632

European-Non Finnish (NFE) AF: 0.298 AC: 78 AN: 262

Other (OTH) AF: 0.247 AC: 49 AN: 198

GnomAD4 genome AF: 0.272 AC: 41287 AN: 151918 Hom.: 6159 Cov.: 31 AF XY: 0.271 AC XY: 20101 AN XY: 74262

African (AFR) AF: 0.169 AC: 7014 AN: 41442

American (AMR) AF: 0.359 AC: 5496 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1463 AN: 3464

East Asian (EAS) AF: 0.122 AC: 626 AN: 5132

South Asian (SAS) AF: 0.274 AC: 1316 AN: 4800

European-Finnish (FIN) AF: 0.263 AC: 2778 AN: 10562

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21622 AN: 67912

Other (OTH) AF: 0.289 AC: 611 AN: 2112

Alfa AF: 0.289 Hom.: 813

Bravo AF: 0.274

Asia WGS AF: 0.202 AC: 703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.37
PhyloP100		0.037
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: rs13299349; hg19: chr9-18573360;