9-18504856-G-A

Variant names:

• chr9-18504856-G-A
• rs779507767
• NM_001040272.6:c.91G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001040272.6(ADAMTSL1):​c.91G>A​(p.Asp31Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000458 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: ADAMTSL1 NM_001040272.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.94
• Publications: 0 publications found

Genes affected

ADAMTSL1 (HGNC:14632): (ADAMTS like 1) This gene encodes a secreted protein and member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) family. This protein lacks the metalloproteinase and disintegrin-like domains, which are typical of the ADAMTS family, but contains other ADAMTS domains, including the thrombospondin type 1 motif. This protein may have important functions in the extracellular matrix. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.099487424).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040272.6. 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
	ADAMTSL1	NM_001040272.6	MANE Select	c.91G>A	p.Asp31Asn	missense	Exon 2 of 29	NP_001035362.3	Q8N6G6-3
	ADAMTSL1	NM_052866.5		c.91G>A	p.Asp31Asn	missense	Exon 2 of 13	NP_443098.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL1	ENST00000380548.9	TSL:5 MANE Select	c.91G>A	p.Asp31Asn	missense	Exon 2 of 29	ENSP00000369921.4	Q8N6G6-3
	ADAMTSL1	ENST00000327883.11	TSL:1	c.91G>A	p.Asp31Asn	missense	Exon 2 of 13	ENSP00000327887.7	Q8N6G6-1
	ADAMTSL1	ENST00000380566.8	TSL:1	c.91G>A	p.Asp31Asn	missense	Exon 2 of 10	ENSP00000369940.4	Q8N6G6-2

Frequencies

GnomAD3 genomes AF: 0.000282 AC: 43 AN: 152240 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000797 AC: 20 AN: 251084 AF XY: 0.0000884

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000550

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000212 AC: 31 AN: 1461742 Hom.: 0 Cov.: 30 AF XY: 0.0000234 AC XY: 17 AN XY: 727170

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

American (AMR) AF: 0.000649 AC: 29 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53360

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111970

Other (OTH) AF: 0.0000166 AC: 1 AN: 60390

GnomAD4 genome AF: 0.000282 AC: 43 AN: 152240 Hom.: 0 Cov.: 32 AF XY: 0.000430 AC XY: 32 AN XY: 74384

African (AFR) AF: 0.0000241 AC: 1 AN: 41466

American (AMR) AF: 0.00275 AC: 42 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000276

ExAC AF: 0.00000824 AC: 1

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	0.20
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	2.0	M
PhyloP100		7.9
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.11
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.99	D
Vest4		0.34
MutPred		0.28		Loss of disorder (P = 0.0976)
MVP		0.70
MPC		0.17
ClinPred		0.18	T
GERP RS		5.4
Varity_R		0.17
gMVP		0.25
Mutation Taster		=40/60	disease causing

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: rs779507767; hg19: chr9-18504854;