rs10888382

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_019032.6(ADAMTSL4):c.2442T>A(p.Asn814Lys) 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 Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N814D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ADAMTSL4
NM_019032.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.94

Publications

20 publications found

Variant links:

Genes affected

ADAMTSL4 (HGNC:19706): (ADAMTS like 4) This gene is a member of ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs)-like gene family and encodes a protein with seven thrombospondin type 1 repeats. The thrombospondin type 1 repeat domain is found in many proteins with diverse biological functions including cellular adhesion, angiogenesis, and patterning of the developing nervous system. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Sep 2014]

ADAMTSL4 Gene-Disease associations (from GenCC):

ectopia lentis 2, isolated, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics
ectopia lentis et pupillae
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
isolated ectopia lentis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ADAMTSL4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31430572).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019032.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ADAMTSL4	NM_019032.6	MANE Select	c.2442T>A	p.Asn814Lys	missense	Exon 15 of 19	NP_061905.2
ADAMTSL4	NM_001288608.2		c.2511T>A	p.Asn837Lys	missense	Exon 16 of 20	NP_001275537.1
ADAMTSL4	NM_001378596.1		c.2442T>A	p.Asn814Lys	missense	Exon 15 of 19	NP_001365525.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ADAMTSL4	ENST00000271643.9	TSL:5 MANE Select	c.2442T>A	p.Asn814Lys	missense	Exon 15 of 19	ENSP00000271643.4
ADAMTSL4	ENST00000369038.6	TSL:1	c.2442T>A	p.Asn814Lys	missense	Exon 13 of 17	ENSP00000358034.2
ADAMTSL4	ENST00000369039.9	TSL:5	c.2511T>A	p.Asn837Lys	missense	Exon 16 of 20	ENSP00000358035.5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.84e-7

AC:

AN:

1461596

Hom.:

Cov.:

100

AF XY:

0.00

AC XY:

AN XY:

727126

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53138

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112002

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.28

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.0044

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.78

M_CAP

Benign

0.027

MetaRNN

Benign

0.31

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.26

PhyloP100

-2.9

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.85

REVEL

Benign

0.029

Sift

Benign

0.92

Sift4G

Benign

0.47

Polyphen

0.12

Vest4

0.30

MutPred

0.46

Gain of ubiquitination at N814 (P = 0.0037)

MVP

0.36

MPC

0.17

ClinPred

0.13

GERP RS

-6.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.055

gMVP

0.13

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over