rs8315

Variant names:

• chr4-185502282-G-A
• rs8315
• NM_014476.6:c.*12C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-185502282-G-A
• chr4-185502282-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_014476.6(PDLIM3):​c.*12C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,613,670 control chromosomes in the GnomAD database, including 164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0093 (17 hom., cov: 33)
  • Exomes 𝑓: 0.012 (147 hom.)
• Consequence: PDLIM3 NM_014476.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.99
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 4-185502282-G-A is Benign according to our data. Variant chr4-185502282-G-A is described in ClinVar as Benign. ClinVar VariationId is 138676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0093 (1414/152124) while in subpopulation SAS AF = 0.0265 (128/4830). AF 95% confidence interval is 0.0228. There are 17 homozygotes in GnomAd4. There are 666 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1414 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDLIM3	NM_014476.6	MANE Select	c.*12C>T		3_prime_UTR	Exon 8 of 8	NP_055291.2
	PDLIM3	NM_001114107.5		c.*12C>T		3_prime_UTR	Exon 7 of 7	NP_001107579.1
	PDLIM3	NM_001257962.2		c.*12C>T		3_prime_UTR	Exon 7 of 7	NP_001244891.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDLIM3	ENST00000284767.12	TSL:5 MANE Select	c.*12C>T		3_prime_UTR	Exon 8 of 8	ENSP00000284767.8
	PDLIM3	ENST00000284771.7	TSL:1	c.*12C>T		3_prime_UTR	Exon 7 of 7	ENSP00000284771.6
	PDLIM3	ENST00000284770.10	TSL:1	c.*12C>T		3_prime_UTR	Exon 5 of 5	ENSP00000284770.5

Frequencies

GnomAD3 genomes AF: 0.00930 AC: 1414 AN: 152006 Hom.: 17 Cov.: 33

Gnomad AFR AF: 0.00233

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.00883

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0263

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0125

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.0111 AC: 2799 AN: 251472 AF XY: 0.0119

Gnomad AFR exome AF: 0.00191

Gnomad AMR exome AF: 0.00607

Gnomad ASJ exome AF: 0.0343

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.00208

Gnomad NFE exome AF: 0.0121

Gnomad OTH exome AF: 0.0107

GnomAD4 exome AF: 0.0119 AC: 17351 AN: 1461546 Hom.: 147 Cov.: 30 AF XY: 0.0122 AC XY: 8891 AN XY: 727108

African (AFR) AF: 0.00239 AC: 80 AN: 33450

American (AMR) AF: 0.00615 AC: 275 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0339 AC: 886 AN: 26130

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39698

South Asian (SAS) AF: 0.0236 AC: 2032 AN: 86246

European-Finnish (FIN) AF: 0.00245 AC: 131 AN: 53418

Middle Eastern (MID) AF: 0.0302 AC: 173 AN: 5724

European-Non Finnish (NFE) AF: 0.0117 AC: 13034 AN: 1111780

Other (OTH) AF: 0.0121 AC: 733 AN: 60376

GnomAD4 genome AF: 0.00930 AC: 1414 AN: 152124 Hom.: 17 Cov.: 33 AF XY: 0.00896 AC XY: 666 AN XY: 74368

African (AFR) AF: 0.00234 AC: 97 AN: 41390

American (AMR) AF: 0.00882 AC: 135 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 111 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0265 AC: 128 AN: 4830

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10610

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0125 AC: 853 AN: 68018

Other (OTH) AF: 0.0128 AC: 27 AN: 2112

Alfa AF: 0.0131 Hom.: 3

Bravo AF: 0.00856

Asia WGS AF: 0.0150 AC: 51 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.82
PhyloP100		-2.0
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: rs8315; hg19: chr4-186423436;