dbSNP rs200191805: ADAMTSL5:p.Arg320Met (chr19-1506822-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_213604.3(ADAMTSL5):c.959G>T(p.Arg320Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000526 in 1,541,136 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00056 ( 1 hom. )

Consequence

ADAMTSL5
NM_213604.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.64

Publications

1 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.

BP4

Computational evidence support a benign effect (MetaRNN=0.09547448).

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.959G>T	p.Arg320Met	missense	Exon 10 of 12	NP_998769.2	X6R4H8
	ADAMTSL5	NM_001367197.1		c.989G>T	p.Arg330Met	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.959G>T	p.Arg320Met	missense	Exon 10 of 12	ENSP00000327608.3	X6R4H8
ADAMTSL5	ENST00000585700.5	TSL:1	n.1037G>T		non_coding_transcript_exon	Exon 10 of 11
ADAMTSL5	ENST00000590440.5	TSL:1	n.997G>T		non_coding_transcript_exon	Exon 10 of 12

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000422

AC:

AN:

142034

AF XY:

0.000381

show subpopulations

Gnomad AFR exome

AF:

0.000133

Gnomad AMR exome

AF:

0.0000958

Gnomad ASJ exome

AF:

0.00117

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000132

Gnomad NFE exome

AF:

0.000641

Gnomad OTH exome

AF:

0.000251

GnomAD4 exome

AF:

0.000557

AC:

774

AN:

1388994

Hom.:

Cov.:

AF XY:

0.000568

AC XY:

389

AN XY:

685318

show subpopulations

African (AFR)

AF:

0.0000323

AC:

AN:

31006

American (AMR)

AF:

0.0000625

AC:

AN:

31996

Ashkenazi Jewish (ASJ)

AF:

0.00122

AC:

AN:

24540

East Asian (EAS)

AF:

0.00

AC:

AN:

35764

South Asian (SAS)

AF:

0.000536

AC:

AN:

78384

European-Finnish (FIN)

AF:

0.000124

AC:

AN:

48270

Middle Eastern (MID)

AF:

0.000745

AC:

AN:

5370

European-Non Finnish (NFE)

AF:

0.000609

AC:

655

AN:

1076150

Other (OTH)

AF:

0.000591

AC:

AN:

57514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

148

198

247

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

<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:

0.000237

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41502

American (AMR)

AF:

0.000131

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000397

AC:

AN:

67956

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.000496

Hom.:

Bravo

AF:

0.000314

ExAC

AF:

0.000247

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Uncertain

0.39

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.063

Eigen

Benign

0.18

Eigen_PC

Benign

0.075

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.60

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.095

MetaSVM

Benign

-0.51

PhyloP100

1.6

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.29

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0050

Vest4

0.50

MVP

0.79

MPC

0.16

ClinPred

0.085

GERP RS

3.0

gMVP

0.66

Mutation Taster

=87/13

polymorphism

(source)

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

Publications

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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