rs11188246

Variant names:

• chr10-95241367-A-G
• rs11188246
• NM_020992.4:c.686-2682T>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.686-2682T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 152,092 control chromosomes in the GnomAD database, including 36,737 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 0.67 (36737 hom., cov: 32)
• Consequence: PDLIM1 NM_020992.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.76
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020992.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDLIM1	NM_020992.4	MANE Select	c.686-2682T>C		intron	N/A	NP_066272.1	O00151

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDLIM1	ENST00000329399.7	TSL:1 MANE Select	c.686-2682T>C		intron	N/A	ENSP00000360305.3	O00151
	PDLIM1	ENST00000956300.1		c.737-2682T>C		intron	N/A	ENSP00000626359.1
	PDLIM1	ENST00000862799.1		c.683-2682T>C		intron	N/A	ENSP00000532858.1

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101714 AN: 151974 Hom.: 36712 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.702

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

GnomAD4 genome AF: 0.669 AC: 101788 AN: 152092 Hom.: 36737 Cov.: 32 AF XY: 0.668 AC XY: 49627 AN XY: 74346

African (AFR) AF: 0.439 AC: 18194 AN: 41474

American (AMR) AF: 0.748 AC: 11429 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2557 AN: 3468

East Asian (EAS) AF: 0.163 AC: 844 AN: 5178

South Asian (SAS) AF: 0.681 AC: 3278 AN: 4814

European-Finnish (FIN) AF: 0.771 AC: 8147 AN: 10572

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.807 AC: 54868 AN: 67986

Other (OTH) AF: 0.699 AC: 1476 AN: 2112

Alfa AF: 0.761 Hom.: 32896

Bravo AF: 0.654

Asia WGS AF: 0.453 AC: 1579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.16
DANN	Benign	0.42
PhyloP100		-2.8
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: rs11188246; hg19: chr10-97001124;