NM_006457.5:c.369G>C

Variant names:

• chr4-94575693-G-C
• NM_006457.5:c.369G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006457.5(PDLIM5):​c.369G>C​(p.Met123Ile) variant causes a missense 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDLIM5 NM_006457.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.56
• Publications: 0 publications found

Genes affected

PDLIM5 (HGNC:17468): (PDZ and LIM domain 5) This gene encodes a member of a family of proteins that possess a 100-amino acid PDZ domain at the N terminus and one to three LIM domains at the C-terminus. This family member functions as a scaffold protein that tethers protein kinases to the Z-disk in striated muscles. It is thought to function in cardiomyocyte expansion and in restraining postsynaptic growth of excitatory synapses. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1711787).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006457.5. 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
	PDLIM5	NM_006457.5	MANE Select	c.369G>C	p.Met123Ile	missense	Exon 5 of 13	NP_006448.5	Q96HC4-1
	PDLIM5	NM_001256428.2		c.3G>C	p.Met1?	start_lost	Exon 4 of 12	NP_001243357.2
	PDLIM5	NM_001256426.2		c.292-250G>C		intron	N/A	NP_001243355.2	Q96HC4-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDLIM5	ENST00000317968.9	TSL:1 MANE Select	c.369G>C	p.Met123Ile	missense	Exon 5 of 13	ENSP00000321746.4	Q96HC4-1
	PDLIM5	ENST00000615540.4	TSL:1	c.292-250G>C		intron	N/A	ENSP00000480359.1	Q96HC4-6
	PDLIM5	ENST00000542407.5	TSL:1	c.292-250G>C		intron	N/A	ENSP00000442187.2	Q96HC4-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.078
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.6
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.10
Sift	Benign	0.40	T
Sift4G	Benign	0.47	T
Polyphen		0.0020	B
Vest4		0.20
MutPred		0.26		Loss of MoRF binding (P = 0.0793)
MVP		0.71
ClinPred		0.50	D
GERP RS		5.1
Varity_R		0.22
Mutation Taster		=23/177	disease causing

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

hg19: chr4-95496844;