rs1049989

Positions:

• chr10-95237722-A-C

Variant summary

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

The NM_020992.4(PDLIM1):​c.*203T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 567,644 control chromosomes in the GnomAD database, including 144,082 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 0.64 (33639 hom., cov: 33)
  • Exomes 𝑓: 0.71 (110443 hom.)
• Consequence: PDLIM1 NM_020992.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDLIM1	NM_020992.4	c.*203T>G		3_prime_UTR_variant	7/7	ENST00000329399.7	NP_066272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDLIM1	ENST00000329399.7	c.*203T>G		3_prime_UTR_variant	7/7	1	NM_020992.4	ENSP00000360305	P1

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96886 AN: 151994 Hom.: 33621 Cov.: 33

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.680

GnomAD4 exome AF: 0.708 AC: 294059 AN: 415532 Hom.: 110443 Cov.: 4 AF XY: 0.711 AC XY: 154044 AN XY: 216710

Gnomad4 AFR exome AF: 0.394

Gnomad4 AMR exome AF: 0.658

Gnomad4 ASJ exome AF: 0.726

Gnomad4 EAS exome AF: 0.151

Gnomad4 SAS exome AF: 0.701

Gnomad4 FIN exome AF: 0.736

Gnomad4 NFE exome AF: 0.788

Gnomad4 OTH exome AF: 0.702

GnomAD4 genome AF: 0.637 AC: 96945 AN: 152112 Hom.: 33639 Cov.: 33 AF XY: 0.635 AC XY: 47241 AN XY: 74356

Gnomad4 AFR AF: 0.397

Gnomad4 AMR AF: 0.677

Gnomad4 ASJ AF: 0.731

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.680

Gnomad4 FIN AF: 0.724

Gnomad4 NFE AF: 0.787

Gnomad4 OTH AF: 0.677

Alfa AF: 0.715 Hom.: 16260

Bravo AF: 0.618

Asia WGS AF: 0.440 AC: 1533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.1
DANN	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1049989; hg19: chr10-96997479; COSMIC: COSV61475376; COSMIC: COSV61475376;