rs3737015

chr10-95268656-A-T

Variant summary

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

The NM_020992.4(PDLIM1):c.333+122T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 710,708 control chromosomes in the GnomAD database, including 203,953 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (38455 hom., cov: 32)
  • Exomes 𝑓: 0.77 (165498 hom.)
• Consequence: PDLIM1 NM_020992.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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 (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDLIM1	NM_020992.4	c.333+122T>A		intron_variant		ENST00000329399.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDLIM1	ENST00000329399.7	c.333+122T>A		intron_variant		1	NM_020992.4	P1
PDLIM1	ENST00000477757.5	n.278+122T>A		intron_variant, non_coding_transcript_variant		2
PDLIM1	ENST00000493949.1	n.607+122T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105990 AN: 151972 Hom.: 38438 Cov.: 32

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.847

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.706

GnomAD4 exome AF: 0.765 AC: 427605 AN: 558618 Hom.: 165498 AF XY: 0.768 AC XY: 230127 AN XY: 299836

Gnomad4 AFR exome AF: 0.498

Gnomad4 AMR exome AF: 0.781

Gnomad4 ASJ exome AF: 0.713

Gnomad4 EAS exome AF: 0.572

Gnomad4 SAS exome AF: 0.747

Gnomad4 FIN exome AF: 0.758

Gnomad4 NFE exome AF: 0.808

Gnomad4 OTH exome AF: 0.741

GnomAD4 genome AF: 0.697 AC: 106045 AN: 152090 Hom.: 38455 Cov.: 32 AF XY: 0.694 AC XY: 51604 AN XY: 74344

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.743

Gnomad4 ASJ AF: 0.711

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.724

Gnomad4 FIN AF: 0.748

Gnomad4 NFE AF: 0.807

Gnomad4 OTH AF: 0.699

Alfa AF: 0.752 Hom.: 5464

Bravo AF: 0.691

Asia WGS AF: 0.631 AC: 2198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.4
Dann	Benign	0.85

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: rs3737015; hg19: chr10-97028413; COSMIC: COSV61474567;