rs17525659

chr10-95247098-T-G

Variant summary

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

The NM_020992.4(PDLIM1):c.685+117A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0959 in 842,894 control chromosomes in the GnomAD database, including 4,660 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 0.083 (684 hom., cov: 33)
  • Exomes 𝑓: 0.099 (3976 hom.)
• Consequence: PDLIM1 NM_020992.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDLIM1	NM_020992.4	c.685+117A>C		intron_variant		ENST00000329399.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDLIM1	ENST00000329399.7	c.685+117A>C		intron_variant		1	NM_020992.4	P1
PDLIM1	ENST00000477757.5	n.630+117A>C		intron_variant, non_coding_transcript_variant		2
PDLIM1	ENST00000490391.1	n.406+117A>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0829 AC: 12611 AN: 152100 Hom.: 684 Cov.: 33

Gnomad AFR AF: 0.0213

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0990

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0408

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.0988 AC: 68269 AN: 690676 Hom.: 3976 AF XY: 0.0978 AC XY: 35062 AN XY: 358386

Gnomad4 AFR exome AF: 0.0191

Gnomad4 AMR exome AF: 0.0746

Gnomad4 ASJ exome AF: 0.0967

Gnomad4 EAS exome AF: 0.0000860

Gnomad4 SAS exome AF: 0.0453

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.0961

GnomAD4 genome AF: 0.0828 AC: 12603 AN: 152218 Hom.: 684 Cov.: 33 AF XY: 0.0823 AC XY: 6127 AN XY: 74424

Gnomad4 AFR AF: 0.0212

Gnomad4 AMR AF: 0.0988

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0406

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0854 Hom.: 93

Bravo AF: 0.0803

Asia WGS AF: 0.0200 AC: 74 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.4
Dann	Benign	0.56

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: rs17525659; hg19: chr10-97006855;