rs2135551

Variant names:

• chr15-84039099-A-G
• rs2135551
• NM_207517.3:c.*1293A>G

Variant summary

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

The NM_207517.3(ADAMTSL3):​c.*1293A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,370 control chromosomes in the GnomAD database, including 3,730 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 0.19 (3717 hom., cov: 32)
  • Exomes 𝑓: 0.28 (13 hom.)
• Consequence: ADAMTSL3 NM_207517.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 22 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]

ENSG00000296726 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL3	NM_207517.3	c.*1293A>G		3_prime_UTR_variant	Exon 30 of 30	ENST00000286744.10	NP_997400.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL3	ENST00000286744.10	c.*1293A>G		3_prime_UTR_variant	Exon 30 of 30	1	NM_207517.3	ENSP00000286744.5

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29622 AN: 151978 Hom.: 3718 Cov.: 32

Gnomad AFR AF: 0.0463

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.0541

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.215

GnomAD4 exome AF: 0.283 AC: 78 AN: 276 Hom.: 13 Cov.: 0 AF XY: 0.265 AC XY: 36 AN XY: 136

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.289 AC: 74 AN: 256

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.188 AC: 3 AN: 16

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.195 AC: 29618 AN: 152094 Hom.: 3717 Cov.: 32 AF XY: 0.194 AC XY: 14438 AN XY: 74346

African (AFR) AF: 0.0462 AC: 1917 AN: 41504

American (AMR) AF: 0.200 AC: 3051 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 956 AN: 3472

East Asian (EAS) AF: 0.0539 AC: 278 AN: 5162

South Asian (SAS) AF: 0.220 AC: 1061 AN: 4824

European-Finnish (FIN) AF: 0.259 AC: 2735 AN: 10550

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18597 AN: 67978

Other (OTH) AF: 0.212 AC: 449 AN: 2114

Alfa AF: 0.258 Hom.: 9191

Bravo AF: 0.184

Asia WGS AF: 0.145 AC: 504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.40
DANN	Benign	0.62
PhyloP100		0.0040
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: rs2135551; hg19: chr15-84707851;