rs2296961

Positions:

• chr10-95263873-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020992.4(PDLIM1):​c.524A>G​(p.Asn175Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,610,756 control chromosomes in the GnomAD database, including 67,499 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.25 (5253 hom., cov: 31)
  • Exomes 𝑓: 0.29 (62246 hom.)
• Consequence: PDLIM1 NM_020992.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.856

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0047923923).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDLIM1	NM_020992.4	c.524A>G	p.Asn175Ser	missense_variant	4/7	ENST00000329399.7	NP_066272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDLIM1	ENST00000329399.7	c.524A>G	p.Asn175Ser	missense_variant	4/7	1	NM_020992.4	ENSP00000360305	P1
PDLIM1	ENST00000477757.5	n.469A>G		non_coding_transcript_exon_variant	3/6	2
PDLIM1	ENST00000493949.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38752 AN: 151914 Hom.: 5255 Cov.: 31

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.0259

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.261

GnomAD3 exomes AF: 0.254 AC: 63090 AN: 248446 Hom.: 8681 AF XY: 0.255 AC XY: 34192 AN XY: 134258

Gnomad AFR exome AF: 0.188

Gnomad AMR exome AF: 0.270

Gnomad ASJ exome AF: 0.248

Gnomad EAS exome AF: 0.0188

Gnomad SAS exome AF: 0.229

Gnomad FIN exome AF: 0.269

Gnomad NFE exome AF: 0.301

Gnomad OTH exome AF: 0.278

GnomAD4 exome AF: 0.287 AC: 418580 AN: 1458724 Hom.: 62246 Cov.: 34 AF XY: 0.286 AC XY: 207374 AN XY: 725522

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.270

Gnomad4 ASJ exome AF: 0.252

Gnomad4 EAS exome AF: 0.0362

Gnomad4 SAS exome AF: 0.229

Gnomad4 FIN exome AF: 0.272

Gnomad4 NFE exome AF: 0.307

Gnomad4 OTH exome AF: 0.269

GnomAD4 genome AF: 0.255 AC: 38766 AN: 152032 Hom.: 5253 Cov.: 31 AF XY: 0.251 AC XY: 18647 AN XY: 74336

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.0261

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.257

Alfa AF: 0.283 Hom.: 3116

Bravo AF: 0.253

TwinsUK AF: 0.312 AC: 1156

ALSPAC AF: 0.299 AC: 1154

ESP6500AA AF: 0.195 AC: 861

ESP6500EA AF: 0.294 AC: 2530

ExAC AF: 0.251 AC: 30496

Asia WGS AF: 0.139 AC: 481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.2
DANN	Benign	0.20
DEOGEN2	Benign	0.085	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.20	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.031
Sift	Benign	1.0	T
Sift4G	Benign	0.87	T
Polyphen		0.0010	B
Vest4		0.068
MPC		0.15
ClinPred		0.0042	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.051
gMVP		0.13

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

Publications

LitVar

Other links and lift over

dbSNP: rs2296961; hg19: chr10-97023630; COSMIC: COSV61474172; COSMIC: COSV61474172;