9-18574183-G-T

Variant names:

• chr9-18574183-G-T
• rs78291060
• NM_001040272.6:c.391G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001040272.6(ADAMTSL1):​c.391G>T​(p.Val131Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000336 in 1,614,120 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: ADAMTSL1 NM_001040272.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.995
• Publications: 2 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011950344).
• BP6: Variant 9-18574183-G-T is Benign according to our data. Variant chr9-18574183-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 786133.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.391G>T	p.Val131Phe	missense	Exon 4 of 29	NP_001035362.3	Q8N6G6-3
	ADAMTSL1	NM_052866.5		c.391G>T	p.Val131Phe	missense	Exon 4 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.391G>T	p.Val131Phe	missense	Exon 4 of 29	ENSP00000369921.4	Q8N6G6-3
	ADAMTSL1	ENST00000327883.11	TSL:1	c.391G>T	p.Val131Phe	missense	Exon 4 of 13	ENSP00000327887.7	Q8N6G6-1
	ADAMTSL1	ENST00000380566.8	TSL:1	c.391G>T	p.Val131Phe	missense	Exon 4 of 10	ENSP00000369940.4	Q8N6G6-2

Frequencies

GnomAD3 genomes AF: 0.00182 AC: 277 AN: 152134 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00611

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

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: 0.00525

GnomAD2 exomes AF: 0.000470 AC: 118 AN: 251294 AF XY: 0.000309

Gnomad AFR exome AF: 0.00621

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000179 AC: 262 AN: 1461868 Hom.: 0 Cov.: 31 AF XY: 0.000161 AC XY: 117 AN XY: 727236

African (AFR) AF: 0.00562 AC: 188 AN: 33480

American (AMR) AF: 0.000581 AC: 26 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111990

Other (OTH) AF: 0.000546 AC: 33 AN: 60396

GnomAD4 genome AF: 0.00184 AC: 280 AN: 152252 Hom.: 2 Cov.: 32 AF XY: 0.00180 AC XY: 134 AN XY: 74440

African (AFR) AF: 0.00616 AC: 256 AN: 41538

American (AMR) AF: 0.000850 AC: 13 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00520 AC: 11 AN: 2116

Alfa AF: 0.000615 Hom.: 2

Bravo AF: 0.00213

ESP6500AA AF: 0.00545 AC: 24

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000535 AC: 65

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.12
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.99
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.033	D
Polyphen		0.81	P
Vest4		0.65
MVP		0.61
MPC		0.24
ClinPred		0.043	T
GERP RS		1.2
Varity_R		0.24
gMVP		0.55
Mutation Taster		=73/27	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

dbSNP: rs78291060; hg19: chr9-18574181;