chr15-83773533-A-G

Variant names:

• chr15-83773533-A-G
• NM_207517.3:c.200A>G

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.200A>G​(p.Asn67Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ADAMTSL3 NM_207517.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03
• 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]

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=0.112886816).

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.200A>G	p.Asn67Ser	missense	Exon 4 of 30	NP_997400.2	P82987-1
	ADAMTSL3	NM_001301110.2		c.200A>G	p.Asn67Ser	missense	Exon 4 of 30	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.200A>G	p.Asn67Ser	missense	Exon 4 of 30	ENSP00000286744.5	P82987-1
	ADAMTSL3	ENST00000567476.1	TSL:1	c.200A>G	p.Asn67Ser	missense	Exon 4 of 30	ENSP00000456313.1	P82987-2
	ADAMTSL3	ENST00000963409.1		c.200A>G	p.Asn67Ser	missense	Exon 4 of 30	ENSP00000633468.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461810 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727214

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111964

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	11
DANN	Benign	0.96
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.20	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.0
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.029
Sift	Benign	0.11	T
Sift4G	Benign	0.21	T
Polyphen		0.13	B
Vest4		0.23
MutPred		0.25		Gain of phosphorylation at N67 (P = 0.0202)
MVP		0.60
MPC		0.13
ClinPred		0.072	T
GERP RS		2.5
Varity_R		0.038
gMVP		0.079
Mutation Taster		=96/4	polymorphism

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

hg19: chr15-84442285;