rs138670107

Variant names:

• chr4-185514281-C-A
• rs138670107
• NM_014476.6:c.387G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-185514281-C-A
• chr4-185514281-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The ENST00000284767.12(PDLIM3):​c.387G>T​(p.Pro129Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P129P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDLIM3 ENST00000284767.12 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.22
• Publications: 3 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP7: Synonymous conserved (PhyloP=2.22 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000284767.12. 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.387G>T	p.Pro129Pro	synonymous	Exon 4 of 8	NP_055291.2
	PDLIM3	NM_001257962.2		c.387G>T	p.Pro129Pro	synonymous	Exon 4 of 7	NP_001244891.1
	PDLIM3	NM_001257963.2		c.150G>T	p.Pro50Pro	synonymous	Exon 2 of 5	NP_001244892.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDLIM3	ENST00000284767.12	TSL:5 MANE Select	c.387G>T	p.Pro129Pro	synonymous	Exon 4 of 8	ENSP00000284767.8
	PDLIM3	ENST00000284770.10	TSL:1	c.150G>T	p.Pro50Pro	synonymous	Exon 2 of 5	ENSP00000284770.5
	PDLIM3	ENST00000504011.5	TSL:1	n.632G>T		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	5.5
DANN	Benign	0.70
PhyloP100		2.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs138670107; hg19: chr4-186435435;