NM_207517.3:c.1468-66C>T

Variant names:

• chr15-83897792-C-T
• rs11259927
• NM_207517.3:c.1468-66C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_207517.3(ADAMTSL3):​c.1468-66C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,490,046 control chromosomes in the GnomAD database, including 47,531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6075 hom., cov: 32)
  • Exomes 𝑓: 0.24 (41456 hom.)
• Consequence: ADAMTSL3 NM_207517.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.106
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 15-83897792-C-T is Benign according to our data. Variant chr15-83897792-C-T is described in ClinVar as Benign. ClinVar VariationId is 1265153.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL3	NM_207517.3	c.1468-66C>T		intron_variant	Intron 13 of 29	ENST00000286744.10	NP_997400.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL3	ENST00000286744.10	c.1468-66C>T		intron_variant	Intron 13 of 29	1	NM_207517.3	ENSP00000286744.5
ADAMTSL3	ENST00000567476.1	c.1468-66C>T		intron_variant	Intron 13 of 29	1		ENSP00000456313.1
ADAMTSL3	ENST00000561483.5	n.1683-66C>T		intron_variant	Intron 13 of 26	5

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40995 AN: 151942 Hom.: 6051 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.239 AC: 319300 AN: 1337986 Hom.: 41456 AF XY: 0.240 AC XY: 157531 AN XY: 656522

African (AFR) AF: 0.304 AC: 9138 AN: 30014

American (AMR) AF: 0.539 AC: 16278 AN: 30206

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 5683 AN: 20646

East Asian (EAS) AF: 0.360 AC: 13793 AN: 38282

South Asian (SAS) AF: 0.371 AC: 24361 AN: 65696

European-Finnish (FIN) AF: 0.203 AC: 9922 AN: 48816

Middle Eastern (MID) AF: 0.183 AC: 965 AN: 5286

European-Non Finnish (NFE) AF: 0.216 AC: 225425 AN: 1044064

Other (OTH) AF: 0.250 AC: 13735 AN: 54976

GnomAD4 genome AF: 0.270 AC: 41072 AN: 152060 Hom.: 6075 Cov.: 32 AF XY: 0.274 AC XY: 20372 AN XY: 74310

African (AFR) AF: 0.308 AC: 12762 AN: 41486

American (AMR) AF: 0.432 AC: 6602 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1006 AN: 3472

East Asian (EAS) AF: 0.361 AC: 1864 AN: 5170

South Asian (SAS) AF: 0.392 AC: 1889 AN: 4816

European-Finnish (FIN) AF: 0.202 AC: 2134 AN: 10550

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14062 AN: 67976

Other (OTH) AF: 0.270 AC: 568 AN: 2104

Alfa AF: 0.231 Hom.: 2301

Bravo AF: 0.287

Asia WGS AF: 0.390 AC: 1354 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.8
DANN	Benign	0.48
PhyloP100		0.11
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: rs11259927; hg19: chr15-84566544; COSMIC: COSV54468250;