4-185502105-G-GT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_014476.6(PDLIM3):c.*188_*189insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00354 in 651,700 control chromosomes in the GnomAD database, including 27 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (21 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (6 hom.)
• Consequence: PDLIM3 NM_014476.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.113

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 4-185502105-G-GT is Benign according to our data. Variant chr4-185502105-G-GT is described in ClinVar as [Likely_benign]. Clinvar id is 1316633.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1538/151678) while in subpopulation AFR AF= 0.0346 (1420/41026). AF 95% confidence interval is 0.0331. There are 21 homozygotes in gnomad4. There are 736 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDLIM3	NM_014476.6	c.*188_*189insA		3_prime_UTR_variant	8/8	ENST00000284767.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDLIM3	ENST00000284767.12	c.*188_*189insA		3_prime_UTR_variant	8/8	5	NM_014476.6	A1
	ENST00000671042.1	n.518-4389dup		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1532 AN: 151562 Hom.: 21 Cov.: 33

Gnomad AFR AF: 0.0346

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.0111

GnomAD4 exome AF: 0.00154 AC: 768 AN: 500022 Hom.: 6 Cov.: 6 AF XY: 0.00125 AC XY: 331 AN XY: 264618

Gnomad4 AFR exome AF: 0.0323

Gnomad4 AMR exome AF: 0.00314

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000322

Gnomad4 SAS exome AF: 0.0000793

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000368

Gnomad4 OTH exome AF: 0.00466

GnomAD4 genome AF: 0.0101 AC: 1538 AN: 151678 Hom.: 21 Cov.: 33 AF XY: 0.00992 AC XY: 736 AN XY: 74176

Gnomad4 AFR AF: 0.0346

Gnomad4 AMR AF: 0.00393

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000485

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00833 Hom.: 4

Bravo AF: 0.0111

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs199939796; hg19: chr4-186423259;