rs11188246

Positions:

• chr10-95241367-A-G

Variant summary

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

The NM_020992.4(PDLIM1):​c.686-2682T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 152,092 control chromosomes in the GnomAD database, including 36,737 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 0.67 (36737 hom., cov: 32)
• Consequence: PDLIM1 NM_020992.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.76

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDLIM1	NM_020992.4	c.686-2682T>C		intron_variant		ENST00000329399.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDLIM1	ENST00000329399.7	c.686-2682T>C		intron_variant		1	NM_020992.4	P1
PDLIM1	ENST00000477757.5	n.631-2682T>C		intron_variant, non_coding_transcript_variant		2
PDLIM1	ENST00000490391.1	n.407-2682T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101714 AN: 151974 Hom.: 36712 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.702

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.669 AC: 101788 AN: 152092 Hom.: 36737 Cov.: 32 AF XY: 0.668 AC XY: 49627 AN XY: 74346

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.681

Gnomad4 FIN AF: 0.771

Gnomad4 NFE AF: 0.807

Gnomad4 OTH AF: 0.699

Alfa AF: 0.761 Hom.: 27260

Bravo AF: 0.654

Asia WGS AF: 0.453 AC: 1579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.16
DANN	Benign	0.42

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: rs11188246; hg19: chr10-97001124;