rs1347296591

Variant names:

• chr15-83655788-G-A
• rs1347296591
• NM_207517.3:c.27G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-83655788-G-A
• chr15-83655788-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_207517.3(ADAMTSL3):​c.27G>A​(p.Trp9*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000479 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ADAMTSL3 NM_207517.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.71
• 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL3	NM_207517.3	c.27G>A	p.Trp9*	stop_gained	Exon 2 of 30	ENST00000286744.10	NP_997400.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL3	ENST00000286744.10	c.27G>A	p.Trp9*	stop_gained	Exon 2 of 30	1	NM_207517.3	ENSP00000286744.5
ADAMTSL3	ENST00000567476.1	c.27G>A	p.Trp9*	stop_gained	Exon 2 of 30	1		ENSP00000456313.1
ADAMTSL3	ENST00000561483.5	n.242G>A		non_coding_transcript_exon_variant	Exon 2 of 27	5
ADAMTSL3	ENST00000569510.5	n.242G>A		non_coding_transcript_exon_variant	Exon 2 of 9	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251238 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461852 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727230

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111982

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.47
CADD	Pathogenic	47
DANN	Uncertain	0.99
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.80	D
PhyloP100		3.7
Vest4		0.14
GERP RS		4.3
Mutation Taster		=21/179	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.90		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.90		Position offset: -4
DS_DL_spliceai		0.26		Position offset: 42

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

Other links and lift over

dbSNP: rs1347296591; hg19: chr15-84324540;