chr15-83913152-T-C

Variant names:

• chr15-83913152-T-C
• rs4842923
• NM_207517.3:c.1761T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 26 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: Benign. The variant received -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 VariationId 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.

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.1761T>C	p.Arg587Arg	synonymous	Exon 16 of 30	NP_997400.2
	ADAMTSL3	NM_001301110.2		c.1761T>C	p.Arg587Arg	synonymous	Exon 16 of 30	NP_001288039.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL3	ENST00000286744.10	TSL:1 MANE Select	c.1761T>C	p.Arg587Arg	synonymous	Exon 16 of 30	ENSP00000286744.5
	ADAMTSL3	ENST00000567476.1	TSL:1	c.1761T>C	p.Arg587Arg	synonymous	Exon 16 of 30	ENSP00000456313.1
	ADAMTSL3	ENST00000963409.1		c.1761T>C	p.Arg587Arg	synonymous	Exon 16 of 30	ENSP00000633468.1

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

GnomAD2 exomes AF: 0.607 AC: 152397 AN: 251166 AF XY: 0.595

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 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

African (AFR) AF: 0.798 AC: 26712 AN: 33478

American (AMR) AF: 0.784 AC: 35046 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 15871 AN: 26136

East Asian (EAS) AF: 0.726 AC: 28809 AN: 39698

South Asian (SAS) AF: 0.609 AC: 52537 AN: 86256

European-Finnish (FIN) AF: 0.510 AC: 27225 AN: 53390

Middle Eastern (MID) AF: 0.659 AC: 3800 AN: 5768

European-Non Finnish (NFE) AF: 0.521 AC: 579569 AN: 1111922

Other (OTH) AF: 0.572 AC: 34516 AN: 60386

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

African (AFR) AF: 0.787 AC: 32598 AN: 41430

American (AMR) AF: 0.708 AC: 10795 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 2142 AN: 3472

East Asian (EAS) AF: 0.744 AC: 3835 AN: 5154

South Asian (SAS) AF: 0.614 AC: 2946 AN: 4800

European-Finnish (FIN) AF: 0.513 AC: 5403 AN: 10536

Middle Eastern (MID) AF: 0.676 AC: 196 AN: 290

European-Non Finnish (NFE) AF: 0.522 AC: 35488 AN: 67926

Other (OTH) AF: 0.615 AC: 1297 AN: 2110

Alfa AF: 0.581 Hom.: 45274

Bravo AF: 0.650

Asia WGS AF: 0.675 AC: 2345 AN: 3478

EpiCase AF: 0.528

EpiControl AF: 0.531

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.96
DANN	Benign	0.45
PhyloP100		-5.2
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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