10-95277821-T-C

Variant names:

• chr10-95277821-T-C
• rs11188256
• NM_020992.4:c.97-6037A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020992.4(PDLIM1):​c.97-6037A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,162 control chromosomes in the GnomAD database, including 3,333 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 0.20 (3333 hom., cov: 32)
• Consequence: PDLIM1 NM_020992.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.483
• Publications: 5 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 (EAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDLIM1	NM_020992.4	c.97-6037A>G		intron_variant	Intron 1 of 6	ENST00000329399.7	NP_066272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDLIM1	ENST00000329399.7	c.97-6037A>G		intron_variant	Intron 1 of 6	1	NM_020992.4	ENSP00000360305.3
PDLIM1	ENST00000477757.5	n.194-8959A>G		intron_variant	Intron 1 of 5	2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29784 AN: 152044 Hom.: 3338 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.196 AC: 29802 AN: 152162 Hom.: 3333 Cov.: 32 AF XY: 0.197 AC XY: 14669 AN XY: 74382

African (AFR) AF: 0.107 AC: 4432 AN: 41542

American (AMR) AF: 0.196 AC: 2998 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 703 AN: 3472

East Asian (EAS) AF: 0.456 AC: 2353 AN: 5162

South Asian (SAS) AF: 0.133 AC: 643 AN: 4820

European-Finnish (FIN) AF: 0.272 AC: 2874 AN: 10574

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15073 AN: 67988

Other (OTH) AF: 0.217 AC: 458 AN: 2114

Alfa AF: 0.214 Hom.: 9731

Bravo AF: 0.195

Asia WGS AF: 0.248 AC: 867 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	1.0
DANN	Benign	0.50
PhyloP100		-0.48
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: rs11188256; hg19: chr10-97037578;