1-150553930-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_019032.6(ADAMTSL4):c.939C>T(p.Gly313Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,609,696 control chromosomes in the GnomAD database, including 68,332 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G313G) has been classified as Benign.

Frequency

Genomes: 𝑓 0.35 ( 10236 hom., cov: 32)

Exomes 𝑓: 0.28 ( 58096 hom. )

Consequence

ADAMTSL4
NM_019032.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.443

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 links:

ADAMTSL4-AS2 (HGNC:40895): (ADAMTSL4 antisense RNA 2)

ADAMTSL4-AS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 1-150553930-C-T is Benign according to our data. Variant chr1-150553930-C-T is described in ClinVar as [Benign]. Clinvar id is 261080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-150553930-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.443 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL4	NM_019032.6 link	c.939C>T	p.Gly313Gly	synonymous_variant	Exon 6 of 19	ENST00000271643.9	NP_061905.2	Q6UY14-1Q9UFG7B7ZMJ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL4	ENST00000271643.9 link	c.939C>T	p.Gly313Gly	synonymous_variant	Exon 6 of 19	5	NM_019032.6	ENSP00000271643.4		Q6UY14-1

Frequencies

GnomAD3 genomes

AF:

0.349

AC:

53033

AN:

151946

Hom.:

10222

Cov.:

show subpopulations

Gnomad AFR

AF:

0.533

Gnomad AMI

AF:

0.210

Gnomad AMR

AF:

0.312

Gnomad ASJ

AF:

0.290

Gnomad EAS

AF:

0.295

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.325

Gnomad MID

AF:

0.242

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.321

GnomAD3 exomes

AF:

0.296

AC:

70318

AN:

237848

Hom.:

10902

AF XY:

0.283

AC XY:

36766

AN XY:

129876

show subpopulations

Gnomad AFR exome

AF:

0.545

Gnomad AMR exome

AF:

0.347

Gnomad ASJ exome

AF:

0.282

Gnomad EAS exome

AF:

0.291

Gnomad SAS exome

AF:

0.200

Gnomad FIN exome

AF:

0.322

Gnomad NFE exome

AF:

0.269

Gnomad OTH exome

AF:

0.296

GnomAD4 exome

AF:

0.278

AC:

405687

AN:

1457632

Hom.:

58096

Cov.:

AF XY:

0.274

AC XY:

198570

AN XY:

724932

show subpopulations

Gnomad4 AFR exome

AF:

0.538

Gnomad4 AMR exome

AF:

0.340

Gnomad4 ASJ exome

AF:

0.281

Gnomad4 EAS exome

AF:

0.327

Gnomad4 SAS exome

AF:

0.197

Gnomad4 FIN exome

AF:

0.315

Gnomad4 NFE exome

AF:

0.270

Gnomad4 OTH exome

AF:

0.291

GnomAD4 genome

AF:

0.349

AC:

53085

AN:

152064

Hom.:

10236

Cov.:

AF XY:

0.348

AC XY:

25860

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.533

Gnomad4 AMR

AF:

0.311

Gnomad4 ASJ

AF:

0.290

Gnomad4 EAS

AF:

0.294

Gnomad4 SAS

AF:

0.187

Gnomad4 FIN

AF:

0.325

Gnomad4 NFE

AF:

0.271

Gnomad4 OTH

AF:

0.319

Alfa

AF:

0.227

Hom.:

947

Bravo

AF:

0.361

Asia WGS

AF:

0.275

AC:

955

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Ectopia lentis 2, isolated, autosomal recessive

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Apr 11, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ectopia lentis et pupillae

Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.0

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over