Genetic Variant PDLIM3:c.*92_*125delTTGTCAACTCCAAATCTAAAGTCAAGGCTTTAGA (chr4-185502168-GTCTAAAGCCTTGACTTTAGATTTGGAGTTGACAA-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_014476.6(PDLIM3):c.*92_*125delTTGTCAACTCCAAATCTAAAGTCAAGGCTTTAGA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00757 in 971,948 control chromosomes in the GnomAD database, including 305 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.026 ( 177 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 128 hom. )

Consequence

PDLIM3
NM_014476.6 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.52

Variant links:

Genes affected

PDLIM3 (HGNC:20767): (PDZ and LIM domain 3) The protein encoded by this gene contains a PDZ domain and a LIM domain, indicating that it may be involved in cytoskeletal assembly. In support of this, the encoded protein has been shown to bind the spectrin-like repeats of alpha-actinin-2 and to colocalize with alpha-actinin-2 at the Z lines of skeletal muscle. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. Aberrant alternative splicing of this gene may play a role in myotonic dystrophy. [provided by RefSeq, Apr 2012]

PDLIM3 links:

ENSG00000249679 (HGNC:):

ENSG00000249679 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 4-185502168-GTCTAAAGCCTTGACTTTAGATTTGGAGTTGACAA-G is Benign according to our data. Variant chr4-185502168-GTCTAAAGCCTTGACTTTAGATTTGGAGTTGACAA-G is described in ClinVar as [Benign]. Clinvar id is 1230235.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDLIM3	NM_014476.6 link	c.92_125delTTGTCAACTCCAAATCTAAAGTCAAGGCTTTAGA		3_prime_UTR_variant	Exon 8 of 8	ENST00000284767.12	NP_055291.2	Q53GG5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDLIM3	ENST00000284767 link	c.92_125delTTGTCAACTCCAAATCTAAAGTCAAGGCTTTAGA		3_prime_UTR_variant	Exon 8 of 8	5	NM_014476.6	ENSP00000284767.8		Q53GG5-1

Frequencies

GnomAD3 genomes

AF:

0.0262

AC:

3989

AN:

152138

Hom.:

176

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0907

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.0201

GnomAD4 exome

AF:

0.00410

AC:

3357

AN:

819692

Hom.:

128

AF XY:

0.00325

AC XY:

1399

AN XY:

430644

show subpopulations

Gnomad4 AFR exome

AF:

0.119

AC:

2698

AN:

22660

Gnomad4 AMR exome

AF:

0.00555

AC:

215

AN:

38704

Gnomad4 ASJ exome

AF:

0.000183

AC:

AN:

21844

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

35314

Gnomad4 SAS exome

AF:

0.000227

AC:

AN:

70598

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

50856

Gnomad4 NFE exome

AF:

0.000160

AC:

AN:

537528

Gnomad4 Remaining exome

AF:

0.00828

AC:

325

AN:

39236

Heterozygous variant carriers

165

330

494

659

824

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<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:

0.0262

AC:

3996

AN:

152256

Hom.:

177

Cov.:

AF XY:

0.0254

AC XY:

1893

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0906

AC:

0.090631

AN:

0.090631

Gnomad4 AMR

AF:

0.0105

AC:

0.0105188

AN:

0.0105188

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000829

AC:

0.0008285

AN:

0.0008285

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000382

AC:

0.000382241

AN:

0.000382241

Gnomad4 OTH

AF:

0.0198

AC:

0.0198488

AN:

0.0198488

Heterozygous variant carriers

181

362

542

723

904

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0231

Hom.:

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 06, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism (auto)

Splicing

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