rs17453855

Variant names:

• chr10-95270620-G-A
• rs17453855
• NM_020992.4:c.248+1013C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PDLIM1	NM_020992.4	c.248+1013C>T		intron_variant	Intron 2 of 6	ENST00000329399.7	NP_066272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDLIM1	ENST00000329399.7	c.248+1013C>T		intron_variant	Intron 2 of 6	1	NM_020992.4	ENSP00000360305.3
PDLIM1	ENST00000477757.5	n.194-1758C>T		intron_variant	Intron 1 of 5	2
PDLIM1	ENST00000493949.1	n.522+1013C>T		intron_variant	Intron 2 of 3	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

African (AFR) AF: 0.0249 AC: 1033 AN: 41478

American (AMR) AF: 0.0474 AC: 725 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0718 AC: 249 AN: 3468

East Asian (EAS) AF: 0.0324 AC: 168 AN: 5180

South Asian (SAS) AF: 0.194 AC: 934 AN: 4814

European-Finnish (FIN) AF: 0.112 AC: 1182 AN: 10578

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0734 AC: 4990 AN: 68004

Other (OTH) AF: 0.0574 AC: 121 AN: 2108

Alfa AF: 0.0671 Hom.: 115

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
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17453855; hg19: chr10-97030377;