rs17453855

Positions:

• chr10-95270620-G-A

Variant summary

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

The NM_020992.4(PDLIM1):​c.248+1013C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0623 in 152,120 control chromosomes in the GnomAD database, including 410 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 0.062 (410 hom., cov: 30)
• Consequence: PDLIM1 NM_020992.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDLIM1	NM_020992.4	c.248+1013C>T		intron_variant		ENST00000329399.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDLIM1	ENST00000329399.7	c.248+1013C>T		intron_variant		1	NM_020992.4	P1
PDLIM1	ENST00000477757.5	n.194-1758C>T		intron_variant, non_coding_transcript_variant		2
PDLIM1	ENST00000493949.1	n.522+1013C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0623 AC: 9471 AN: 152002 Hom.: 409 Cov.: 30

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0475

Gnomad ASJ AF: 0.0718

Gnomad EAS AF: 0.0324

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0734

Gnomad OTH AF: 0.0570

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

GnomAD4 genome AF: 0.0623 AC: 9479 AN: 152120 Hom.: 410 Cov.: 30 AF XY: 0.0657 AC XY: 4883 AN XY: 74368

Gnomad4 AFR AF: 0.0249

Gnomad4 AMR AF: 0.0474

Gnomad4 ASJ AF: 0.0718

Gnomad4 EAS AF: 0.0324

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.0734

Gnomad4 OTH AF: 0.0574

Alfa AF: 0.0672 Hom.: 46

Bravo AF: 0.0531

Asia WGS AF: 0.122 AC: 423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.60
DANN	Benign	0.43

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: rs17453855; hg19: chr10-97030377;