4-185502205-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_014476.6(PDLIM3):c.*89A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,329,556 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (17 hom., cov: 33)
  • Exomes 𝑓: 0.012 (127 hom.)
• Consequence: PDLIM3 NM_014476.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.616

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 4-185502205-T-C is Benign according to our data. Variant chr4-185502205-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1318143.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00996 (1517/152360) while in subpopulation SAS AF= 0.0265 (128/4832). AF 95% confidence interval is 0.0228. There are 17 homozygotes in gnomad4. There are 718 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDLIM3	NM_014476.6	c.*89A>G		3_prime_UTR_variant	8/8	ENST00000284767.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDLIM3	ENST00000284767.12	c.*89A>G		3_prime_UTR_variant	8/8	5	NM_014476.6	A1
	ENST00000671042.1	n.518-4296T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00996 AC: 1516 AN: 152242 Hom.: 17 Cov.: 33

Gnomad AFR AF: 0.00463

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.00929

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0263

Gnomad FIN AF: 0.00169

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0125

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.0117 AC: 13830 AN: 1177196 Hom.: 127 Cov.: 17 AF XY: 0.0121 AC XY: 7279 AN XY: 599198

Gnomad4 AFR exome AF: 0.00464

Gnomad4 AMR exome AF: 0.00622

Gnomad4 ASJ exome AF: 0.0338

Gnomad4 EAS exome AF: 0.000182

Gnomad4 SAS exome AF: 0.0231

Gnomad4 FIN exome AF: 0.00246

Gnomad4 NFE exome AF: 0.0116

Gnomad4 OTH exome AF: 0.0121

GnomAD4 genome AF: 0.00996 AC: 1517 AN: 152360 Hom.: 17 Cov.: 33 AF XY: 0.00964 AC XY: 718 AN XY: 74512

Gnomad4 AFR AF: 0.00467

Gnomad4 AMR AF: 0.00927

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0265

Gnomad4 FIN AF: 0.00169

Gnomad4 NFE AF: 0.0125

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.0105 Hom.: 1

Bravo AF: 0.00934

Asia WGS AF: 0.0150 AC: 51 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 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.72
Dann	Benign	0.53

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: rs1801942; hg19: chr4-186423359;