NM_207517.3:c.1981G>C

Variant names:

• chr15-83913372-G-C
• NM_207517.3:c.1981G>C
• ADAMTSL3 p.Val661Leu

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_207517.3(ADAMTSL3):​c.1981G>C​(p.Val661Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ADAMTSL3 NM_207517.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060324788).

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.1981G>C	p.Val661Leu	missense	Exon 16 of 30	NP_997400.2	P82987-1
	ADAMTSL3	NM_001301110.2		c.1981G>C	p.Val661Leu	missense	Exon 16 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.1981G>C	p.Val661Leu	missense	Exon 16 of 30	ENSP00000286744.5	P82987-1
	ADAMTSL3	ENST00000567476.1	TSL:1	c.1981G>C	p.Val661Leu	missense	Exon 16 of 30	ENSP00000456313.1	P82987-2
	ADAMTSL3	ENST00000963409.1		c.1981G>C	p.Val661Leu	missense	Exon 16 of 30	ENSP00000633468.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.7
DANN	Benign	0.88
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.080	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.4	N
PhyloP100		0.25
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.22	N
REVEL	Benign	0.19
Sift	Benign	0.23	T
Sift4G	Benign	0.23	T
Varity_R		0.058
gMVP		0.21

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr15-84582124;