NM_014476.6:c.*188dupA

Variant names:

• chr4-185502105-G-GT
• rs199939796
• NM_014476.6:c.*188dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_014476.6(PDLIM3):​c.*188dupA 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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• dilated cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000249679 (HGNC:58917):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1538 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014476.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDLIM3	NM_014476.6	MANE Select	c.*188dupA		3_prime_UTR	Exon 8 of 8	NP_055291.2	Q53GG5-1
	PDLIM3	NM_001114107.5		c.*188dupA		3_prime_UTR	Exon 7 of 7	NP_001107579.1	Q53GG5-2
	PDLIM3	NM_001257962.2		c.*188dupA		3_prime_UTR	Exon 7 of 7	NP_001244891.1	A0A087WYF8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDLIM3	ENST00000284767.12	TSL:5 MANE Select	c.*188dupA		3_prime_UTR	Exon 8 of 8	ENSP00000284767.8	Q53GG5-1
	PDLIM3	ENST00000284771.7	TSL:1	c.*188dupA		3_prime_UTR	Exon 7 of 7	ENSP00000284771.6	Q53GG5-2
	PDLIM3	ENST00000284770.10	TSL:1	c.*188dupA		3_prime_UTR	Exon 5 of 5	ENSP00000284770.5	A0A2U3TZH4

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

African (AFR) AF: 0.0323 AC: 439 AN: 13574

American (AMR) AF: 0.00314 AC: 78 AN: 24842

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15880

East Asian (EAS) AF: 0.0000322 AC: 1 AN: 31038

South Asian (SAS) AF: 0.0000793 AC: 4 AN: 50440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35368

Middle Eastern (MID) AF: 0.00330 AC: 7 AN: 2122

European-Non Finnish (NFE) AF: 0.000368 AC: 110 AN: 299076

Other (OTH) AF: 0.00466 AC: 129 AN: 27682

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

African (AFR) AF: 0.0346 AC: 1420 AN: 41026

American (AMR) AF: 0.00393 AC: 60 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000485 AC: 33 AN: 67996

Other (OTH) AF: 0.0109 AC: 23 AN: 2102

Alfa AF: 0.00833 Hom.: 4

Bravo AF: 0.0111

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs199939796; hg19: chr4-186423259;