15-84037709-C-A

Variant names:

• chr15-84037709-C-A
• rs950169
• NM_207517.3:c.4979C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207517.3(ADAMTSL3):​c.4979C>A​(p.Thr1660Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1660I) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ADAMTSL3 NM_207517.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.54
• Publications: 0 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]

ENSG00000296726 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.069521934).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL3	NM_207517.3	MANE Select	c.4979C>A	p.Thr1660Lys	missense	Exon 30 of 30	NP_997400.2	P82987-1
	ADAMTSL3	NM_001301110.2		c.4987-54C>A		intron	N/A	NP_001288039.1	P82987-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL3	ENST00000286744.10	TSL:1 MANE Select	c.4979C>A	p.Thr1660Lys	missense	Exon 30 of 30	ENSP00000286744.5	P82987-1
	ADAMTSL3	ENST00000567476.1	TSL:1	c.4987-54C>A		intron	N/A	ENSP00000456313.1	P82987-2
	ADAMTSL3	ENST00000963409.1		c.4970-54C>A		intron	N/A	ENSP00000633468.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450976 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 721514

African (AFR) AF: 0.00 AC: 0 AN: 32776

American (AMR) AF: 0.00 AC: 0 AN: 41528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25634

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83588

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108862

Other (OTH) AF: 0.00 AC: 0 AN: 59964

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.4
DANN	Benign	0.72
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.5
PrimateAI	Benign	0.33	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.094
Sift	Benign	1.0	T
Sift4G	Benign	0.93	T
Polyphen		0.0	B
Vest4		0.079
MutPred		0.49		Gain of methylation at T1660 (P = 0.0011)
MVP		0.34
MPC		0.15
ClinPred		0.38	T
GERP RS		-0.022
Varity_R		0.085
gMVP		0.11

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: rs950169; hg19: chr15-84706461;