chr4-94573370-C-G

Variant names:

• chr4-94573370-C-G
• rs898744312
• NM_006457.5:c.268C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006457.5(PDLIM5):​c.268C>G​(p.Pro90Ala) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P90S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDLIM5 NM_006457.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.978

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12588745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDLIM5	NM_006457.5	c.268C>G	p.Pro90Ala	missense_variant	Exon 4 of 13	ENST00000317968.9	NP_006448.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDLIM5	ENST00000317968.9	c.268C>G	p.Pro90Ala	missense_variant	Exon 4 of 13	1	NM_006457.5	ENSP00000321746.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251326 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135842

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.29	.;.;.;T;.;.;.;.;.
Eigen	Benign	-0.052
Eigen_PC	Benign	-0.0018
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.90	D;D;D;D;D;D;.;.;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.13	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L;L;L;L;L;L;L;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.5	N;N;.;N;N;.;N;N;.
REVEL	Benign	0.016
Sift	Benign	0.15	T;T;.;T;T;.;T;T;.
Sift4G	Benign	0.23	T;T;T;T;T;T;T;T;T
Polyphen		0.0	B;B;.;B;.;B;B;.;.
Vest4		0.26
MutPred		0.17		Loss of glycosylation at P90 (P = 0.0449);Loss of glycosylation at P90 (P = 0.0449);Loss of glycosylation at P90 (P = 0.0449);Loss of glycosylation at P90 (P = 0.0449);Loss of glycosylation at P90 (P = 0.0449);Loss of glycosylation at P90 (P = 0.0449);Loss of glycosylation at P90 (P = 0.0449);Loss of glycosylation at P90 (P = 0.0449);.;
MVP		0.61
MPC		0.11
ClinPred		0.098	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.051
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs898744312; hg19: chr4-95494521;