rs11188249

Variant names:

• chr10-95250622-A-G
• rs11188249
• NM_020992.4:c.534-3256T>C

Variant summary

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

The NM_020992.4(PDLIM1):​c.534-3256T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0746 in 152,314 control chromosomes in the GnomAD database, including 603 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 0.075 (603 hom., cov: 32)
• Consequence: PDLIM1 NM_020992.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDLIM1	NM_020992.4	c.534-3256T>C		intron_variant	Intron 4 of 6	ENST00000329399.7	NP_066272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDLIM1	ENST00000329399.7	c.534-3256T>C		intron_variant	Intron 4 of 6	1	NM_020992.4	ENSP00000360305.3
PDLIM1	ENST00000477757.5	n.479-3256T>C		intron_variant	Intron 3 of 5	2

Frequencies

GnomAD3 genomes AF: 0.0747 AC: 11362 AN: 152196 Hom.: 603 Cov.: 32

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0501

Gnomad FIN AF: 0.0629

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0616

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

GnomAD4 genome AF: 0.0746 AC: 11361 AN: 152314 Hom.: 603 Cov.: 32 AF XY: 0.0726 AC XY: 5411 AN XY: 74488

African (AFR) AF: 0.0186 AC: 772 AN: 41576

American (AMR) AF: 0.128 AC: 1957 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 171 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5188

South Asian (SAS) AF: 0.0501 AC: 242 AN: 4828

European-Finnish (FIN) AF: 0.0629 AC: 667 AN: 10606

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7276 AN: 68028

Other (OTH) AF: 0.0610 AC: 129 AN: 2116

Alfa AF: 0.0926 Hom.: 1040

Bravo AF: 0.0757

Asia WGS AF: 0.0250 AC: 88 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.5
DANN	Benign	0.84
PhyloP100		0.27
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: rs11188249; hg19: chr10-97010379;