NM_207517.3:c.4755-1176A>G

Variant names:

• chr15-84035597-A-G
• rs17299684
• NM_207517.3:c.4755-1176A>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.4755-1176A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,260 control chromosomes in the GnomAD database, including 1,269 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 0.12 (1269 hom., cov: 32)
• Consequence: ADAMTSL3 NM_207517.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL3	NM_207517.3	MANE Select	c.4755-1176A>G		intron	N/A	NP_997400.2
	ADAMTSL3	NM_001301110.2		c.4755-1176A>G		intron	N/A	NP_001288039.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL3	ENST00000286744.10	TSL:1 MANE Select	c.4755-1176A>G		intron	N/A	ENSP00000286744.5
	ADAMTSL3	ENST00000567476.1	TSL:1	c.4755-1176A>G		intron	N/A	ENSP00000456313.1
	ENSG00000296726	ENST00000741322.1		n.143+44448T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18100 AN: 152142 Hom.: 1269 Cov.: 32

Gnomad AFR AF: 0.0693

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0916

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0605

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.120

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.119 AC: 18099 AN: 152260 Hom.: 1269 Cov.: 32 AF XY: 0.117 AC XY: 8709 AN XY: 74434

African (AFR) AF: 0.0692 AC: 2877 AN: 41574

American (AMR) AF: 0.0914 AC: 1398 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 578 AN: 3470

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5178

South Asian (SAS) AF: 0.0599 AC: 289 AN: 4826

European-Finnish (FIN) AF: 0.187 AC: 1985 AN: 10600

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10625 AN: 68000

Other (OTH) AF: 0.119 AC: 252 AN: 2114

Alfa AF: 0.138 Hom.: 4928

Bravo AF: 0.110

Asia WGS AF: 0.0270 AC: 93 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.4
DANN	Benign	0.71
PhyloP100		0.084
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: rs17299684; hg19: chr15-84704349;