10-95247317-C-T

Variant names:

• chr10-95247317-C-T
• NM_020992.4:c.583G>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020992.4(PDLIM1):​c.583G>A​(p.Glu195Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PDLIM1 NM_020992.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

Genes affected

PDLIM1 (HGNC:2067): (PDZ and LIM domain 1) This gene encodes a member of the enigma protein family. The protein contains two protein interacting domains, a PDZ domain at the amino terminal end and one to three LIM domains at the carboxyl terminal. It is a cytoplasmic protein associated with the cytoskeleton. The protein may function as an adapter to bring other LIM-interacting proteins to the cytoskeleton. Pseudogenes associated with this gene are located on chromosomes 3, 14 and 17. [provided by RefSeq, Oct 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.796

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDLIM1	NM_020992.4	c.583G>A	p.Glu195Lys	missense_variant	Exon 5 of 7	ENST00000329399.7	NP_066272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDLIM1	ENST00000329399.7	c.583G>A	p.Glu195Lys	missense_variant	Exon 5 of 7	1	NM_020992.4	ENSP00000360305.3
PDLIM1	ENST00000477757.5	n.528G>A		non_coding_transcript_exon_variant	Exon 4 of 6	2
PDLIM1	ENST00000490391.1	n.304G>A		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.583G>A (p.E195K) alteration is located in exon 5 (coding exon 5) of the PDLIM1 gene. This alteration results from a G to A substitution at nucleotide position 583, causing the glutamic acid (E) at amino acid position 195 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.46	T
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.082	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.40	T
MutationAssessor	Pathogenic	3.2	M
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.25
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.80
MutPred		0.35		Gain of methylation at E195 (P = 0.0121);
MVP		0.80
MPC		0.69
ClinPred		0.99	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.82
gMVP		0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-97007074;