rs4842923

Positions:

• chr15-83913152-T-C
• chr15-83913152-T-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_207517.3(ADAMTSL3):​c.1761T>C​(p.Arg587Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,613,638 control chromosomes in the GnomAD database, including 256,099 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (30951 hom., cov: 31)
  • Exomes 𝑓: 0.55 (225148 hom.)
• Consequence: ADAMTSL3 NM_207517.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.18

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]

ADAMTSL3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 15-83913152-T-C is Benign according to our data. Variant chr15-83913152-T-C is described in ClinVar as [Benign]. Clinvar id is 1224999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.18 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTSL3	NM_207517.3	c.1761T>C	p.Arg587Arg	synonymous_variant	16/30	ENST00000286744.10	NP_997400.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTSL3	ENST00000286744.10	c.1761T>C	p.Arg587Arg	synonymous_variant	16/30	1	NM_207517.3	ENSP00000286744.5
ADAMTSL3	ENST00000567476.1	c.1761T>C	p.Arg587Arg	synonymous_variant	16/30	1		ENSP00000456313.1
ADAMTSL3	ENST00000561483.5	n.1976T>C		non_coding_transcript_exon_variant	16/27	5

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95115 AN: 151764 Hom.: 30903 Cov.: 31

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.670

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.616

GnomAD3 exomes AF: 0.607 AC: 152397 AN: 251166 Hom.: 48024 AF XY: 0.595 AC XY: 80756 AN XY: 135758

Gnomad AFR exome AF: 0.793

Gnomad AMR exome AF: 0.795

Gnomad ASJ exome AF: 0.614

Gnomad EAS exome AF: 0.745

Gnomad SAS exome AF: 0.603

Gnomad FIN exome AF: 0.514

Gnomad NFE exome AF: 0.520

Gnomad OTH exome AF: 0.570

GnomAD4 exome AF: 0.550 AC: 804085 AN: 1461756 Hom.: 225148 Cov.: 66 AF XY: 0.550 AC XY: 399950 AN XY: 727182

Gnomad4 AFR exome AF: 0.798

Gnomad4 AMR exome AF: 0.784

Gnomad4 ASJ exome AF: 0.607

Gnomad4 EAS exome AF: 0.726

Gnomad4 SAS exome AF: 0.609

Gnomad4 FIN exome AF: 0.510

Gnomad4 NFE exome AF: 0.521

Gnomad4 OTH exome AF: 0.572

GnomAD4 genome AF: 0.627 AC: 95225 AN: 151882 Hom.: 30951 Cov.: 31 AF XY: 0.628 AC XY: 46651 AN XY: 74246

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.708

Gnomad4 ASJ AF: 0.617

Gnomad4 EAS AF: 0.744

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.513

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.615

Alfa AF: 0.561 Hom.: 32315

Bravo AF: 0.650

Asia WGS AF: 0.675 AC: 2345 AN: 3478

EpiCase AF: 0.528

EpiControl AF: 0.531

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.96
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4842923; hg19: chr15-84581904; COSMIC: COSV54448135;