rs11872

Positions:

• chr10-95237852-G-A
• chr10-95237852-G-C

Variant summary

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

The NM_020992.4(PDLIM1):​c.*73C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.062 in 1,317,924 control chromosomes in the GnomAD database, including 3,274 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 0.048 (253 hom., cov: 32)
  • Exomes 𝑓: 0.064 (3021 hom.)
• Consequence: PDLIM1 NM_020992.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.627

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDLIM1	NM_020992.4	c.*73C>T		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.*73C>T		3_prime_UTR_variant	7/7	1	NM_020992.4	ENSP00000360305	P1

Frequencies

GnomAD3 genomes AF: 0.0481 AC: 7313 AN: 152092 Hom.: 252 Cov.: 32

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0352

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.0426

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0601

Gnomad OTH AF: 0.0363

GnomAD4 exome AF: 0.0638 AC: 74402 AN: 1165714 Hom.: 3021 Cov.: 15 AF XY: 0.0665 AC XY: 38704 AN XY: 582290

Gnomad4 AFR exome AF: 0.00798

Gnomad4 AMR exome AF: 0.0223

Gnomad4 ASJ exome AF: 0.0270

Gnomad4 EAS exome AF: 0.0387

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.0982

Gnomad4 NFE exome AF: 0.0606

Gnomad4 OTH exome AF: 0.0596

GnomAD4 genome AF: 0.0480 AC: 7312 AN: 152210 Hom.: 253 Cov.: 32 AF XY: 0.0513 AC XY: 3822 AN XY: 74436

Gnomad4 AFR AF: 0.0101

Gnomad4 AMR AF: 0.0351

Gnomad4 ASJ AF: 0.0282

Gnomad4 EAS AF: 0.0425

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.0601

Gnomad4 OTH AF: 0.0364

Alfa AF: 0.0521 Hom.: 29

Bravo AF: 0.0395

Asia WGS AF: 0.103 AC: 356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.8
DANN	Benign	0.46
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0

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: rs11872; hg19: chr10-96997609; COSMIC: COSV61474917; COSMIC: COSV61474917;