chr15-83704489-C-A

Variant names:

• chr15-83704489-C-A
• NM_207517.3:c.170C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_207517.3(ADAMTSL3):​c.170C>A​(p.Thr57Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,878 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ADAMTSL3 NM_207517.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.08

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL3	NM_207517.3	c.170C>A	p.Thr57Asn	missense_variant	Exon 3 of 30	ENST00000286744.10	NP_997400.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL3	ENST00000286744.10	c.170C>A	p.Thr57Asn	missense_variant	Exon 3 of 30	1	NM_207517.3	ENSP00000286744.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461878 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727232

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	T;.
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.065	D
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	0.90	L;L
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.7	N;N
REVEL	Uncertain	0.37
Sift	Uncertain	0.014	D;D
Sift4G	Uncertain	0.053	T;D
Polyphen		1.0	D;D
Vest4		0.78
MutPred		0.60		Loss of phosphorylation at T57 (P = 0.0634);Loss of phosphorylation at T57 (P = 0.0634);
MVP		0.77
MPC		0.59
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.25
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-84373241;