rs112661328

Variant names:

• chr4-185525103-G-A
• rs112661328
• NM_014476.6:c.162C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-185525103-G-A
• chr4-185525103-G-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_014476.6(PDLIM3):​c.162C>T​(p.Gly54Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00994 in 1,614,126 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0071 (7 hom., cov: 33)
  • Exomes 𝑓: 0.010 (99 hom.)
• Consequence: PDLIM3 NM_014476.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 1.74
• Publications: 5 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:):

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 4-185525103-G-A is Benign according to our data. Variant chr4-185525103-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 138668.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.74 with no splicing effect.
• BS2: High AC in GnomAd4 at 1077 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.162C>T	p.Gly54Gly	synonymous	Exon 2 of 8	NP_055291.2
	PDLIM3	NM_001114107.5		c.162C>T	p.Gly54Gly	synonymous	Exon 2 of 7	NP_001107579.1
	PDLIM3	NM_001257962.2		c.162C>T	p.Gly54Gly	synonymous	Exon 2 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.162C>T	p.Gly54Gly	synonymous	Exon 2 of 8	ENSP00000284767.8
	PDLIM3	ENST00000284771.7	TSL:1	c.162C>T	p.Gly54Gly	synonymous	Exon 2 of 7	ENSP00000284771.6
	PDLIM3	ENST00000504011.5	TSL:1	n.219C>T		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes AF: 0.00707 AC: 1076 AN: 152204 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00234

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00662

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.0119

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.00955

GnomAD2 exomes AF: 0.00799 AC: 2008 AN: 251356 AF XY: 0.00783

Gnomad AFR exome AF: 0.00234

Gnomad AMR exome AF: 0.00489

Gnomad ASJ exome AF: 0.00784

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0157

Gnomad NFE exome AF: 0.0110

Gnomad OTH exome AF: 0.00619

GnomAD4 exome AF: 0.0102 AC: 14971 AN: 1461804 Hom.: 99 Cov.: 31 AF XY: 0.00986 AC XY: 7167 AN XY: 727212

African (AFR) AF: 0.00167 AC: 56 AN: 33478

American (AMR) AF: 0.00505 AC: 226 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00800 AC: 209 AN: 26136

East Asian (EAS) AF: 0.000353 AC: 14 AN: 39698

South Asian (SAS) AF: 0.00315 AC: 272 AN: 86258

European-Finnish (FIN) AF: 0.0166 AC: 885 AN: 53416

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5768

European-Non Finnish (NFE) AF: 0.0115 AC: 12785 AN: 1111940

Other (OTH) AF: 0.00853 AC: 515 AN: 60388

GnomAD4 genome AF: 0.00707 AC: 1077 AN: 152322 Hom.: 7 Cov.: 33 AF XY: 0.00709 AC XY: 528 AN XY: 74488

African (AFR) AF: 0.00233 AC: 97 AN: 41572

American (AMR) AF: 0.00386 AC: 59 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00662 AC: 23 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4828

European-Finnish (FIN) AF: 0.0119 AC: 126 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0106 AC: 721 AN: 68020

Other (OTH) AF: 0.00945 AC: 20 AN: 2116

Alfa AF: 0.00901 Hom.: 1

Bravo AF: 0.00667

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00911

EpiControl AF: 0.00954

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	2	not provided (2)
-	-	1	Primary dilated cardiomyopathy;C0007194:Hypertrophic cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	11
DANN	Benign	0.85
PhyloP100		1.7
Mutation Taster		=99/1	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: rs112661328; hg19: chr4-186446257;