15-83804753-A-C

Variant names:

• chr15-83804753-A-C
• rs28504011
• NM_207517.3:c.363+58A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_207517.3(ADAMTSL3):​c.363+58A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000847 in 1,180,502 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 30)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: ADAMTSL3 NM_207517.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• 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: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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.363+58A>C		intron	N/A	NP_997400.2	P82987-1
	ADAMTSL3	NM_001301110.2		c.363+58A>C		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.363+58A>C		intron	N/A	ENSP00000286744.5	P82987-1
	ADAMTSL3	ENST00000567476.1	TSL:1	c.363+58A>C		intron	N/A	ENSP00000456313.1	P82987-2
	ADAMTSL3	ENST00000963409.1		c.363+58A>C		intron	N/A	ENSP00000633468.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 8.47e-7 AC: 1 AN: 1180502 Hom.: 0 AF XY: 0.00000169 AC XY: 1 AN XY: 590756

African (AFR) AF: 0.00 AC: 0 AN: 25326

American (AMR) AF: 0.00 AC: 0 AN: 23708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22388

East Asian (EAS) AF: 0.00 AC: 0 AN: 34926

South Asian (SAS) AF: 0.00 AC: 0 AN: 64888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50052

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4910

European-Non Finnish (NFE) AF: 0.00000111 AC: 1 AN: 904348

Other (OTH) AF: 0.00 AC: 0 AN: 49956

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.0
DANN	Benign	0.58
PhyloP100		1.4

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: rs28504011; hg19: chr15-84473505;