dbSNP rs753752128: ADAMTSL5:p.Ala333Thr (chr19-1506784-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_213604.3(ADAMTSL5):c.997G>A(p.Ala333Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000022 in 1,542,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

ADAMTSL5
NM_213604.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0270

Publications

0 publications found

Variant links:

Genes affected

ADAMTSL5 (HGNC:27912): (ADAMTS like 5) Enables heparin binding activity and microfibril binding activity. Located in extracellular region and microfibril. [provided by Alliance of Genome Resources, Apr 2022]

ADAMTSL5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.026218832).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213604.3. 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
	ADAMTSL5	NM_213604.3	MANE Select	c.997G>A	p.Ala333Thr	missense	Exon 10 of 12	NP_998769.2	X6R4H8
	ADAMTSL5	NM_001367197.1		c.1027G>A	p.Ala343Thr	missense	Exon 11 of 13	NP_001354126.1	Q6ZMM2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADAMTSL5	ENST00000330475.9	TSL:2 MANE Select	c.997G>A	p.Ala333Thr	missense	Exon 10 of 12	ENSP00000327608.3	X6R4H8
ADAMTSL5	ENST00000585700.5	TSL:1	n.1075G>A		non_coding_transcript_exon	Exon 10 of 11
ADAMTSL5	ENST00000590440.5	TSL:1	n.1035G>A		non_coding_transcript_exon	Exon 10 of 12

Frequencies

GnomAD3 genomes

AF:

0.0000462

AC:

AN:

151596

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000279

AC:

AN:

143146

AF XY:

0.0000130

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000148

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000898

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000194

AC:

AN:

1390480

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

686238

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31274

American (AMR)

AF:

0.000126

AC:

AN:

31640

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24358

East Asian (EAS)

AF:

0.0000826

AC:

AN:

36322

South Asian (SAS)

AF:

0.0000891

AC:

AN:

78576

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5150

European-Non Finnish (NFE)

AF:

0.0000121

AC:

AN:

1077108

Other (OTH)

AF:

0.00

AC:

AN:

57456

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000462

AC:

AN:

151596

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74004

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41218

American (AMR)

AF:

0.00

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000195

AC:

AN:

5124

South Asian (SAS)

AF:

0.00

AC:

AN:

4790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67876

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.546

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000281

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.60

CADD

Benign

3.2

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.0065

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.59

M_CAP

Benign

0.015

MetaRNN

Benign

0.026

MetaSVM

Benign

-1.0

PhyloP100

0.027

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.54

REVEL

Benign

0.022

Sift

Benign

0.59

Sift4G

Benign

0.27

Vest4

0.16

MVP

0.13

MPC

0.10

ClinPred

0.012

GERP RS

1.2

gMVP

0.19

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over