Genetic Variant ADAMTSL3:c.364-135_364-132delAAAA (chr15-83819661-CAAAA-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS1

The NM_207517.3(ADAMTSL3):c.364-135_364-132delAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 506,416 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 0)

Exomes 𝑓: 0.018 ( 0 hom. )

Consequence

ADAMTSL3
NM_207517.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.436

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0184 (7110/385956) while in subpopulation SAS AF= 0.0331 (1175/35486). AF 95% confidence interval is 0.0315. There are 0 homozygotes in gnomad4_exome. There are 3834 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL3	NM_207517.3 link	c.364-135_364-132delAAAA		intron_variant	Intron 5 of 29	ENST00000286744.10	NP_997400.2	P82987-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL3	ENST00000286744.10 link	c.364-149_364-146delAAAA		intron_variant	Intron 5 of 29	1	NM_207517.3	ENSP00000286744.5		P82987-1

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

120460

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000235

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00186

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000123

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0184

AC:

7110

AN:

385956

Hom.:

AF XY:

0.0190

AC XY:

3834

AN XY:

202172

show subpopulations

Gnomad4 AFR exome

AF:

0.0104

Gnomad4 AMR exome

AF:

0.0170

Gnomad4 ASJ exome

AF:

0.0160

Gnomad4 EAS exome

AF:

0.0158

Gnomad4 SAS exome

AF:

0.0331

Gnomad4 FIN exome

AF:

0.0165

Gnomad4 NFE exome

AF:

0.0175

Gnomad4 OTH exome

AF:

0.0169

GnomAD4 genome

AF:

0.000158

AC:

AN:

120460

Hom.:

Cov.:

AF XY:

0.000210

AC XY:

AN XY:

57148

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000235

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00186

Gnomad4 NFE

AF:

0.000123

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

15-83819661-CAAAAAAA-CAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over