NM_020992.4:c.685+117A>C

Variant names:

• chr10-95247098-T-G
• rs17525659
• NM_020992.4:c.685+117A>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.685+117A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0959 in 842,894 control chromosomes in the GnomAD database, including 4,660 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 0.083 (684 hom., cov: 33)
  • Exomes 𝑓: 0.099 (3976 hom.)
• Consequence: PDLIM1 NM_020992.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.115 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDLIM1	NM_020992.4	MANE Select	c.685+117A>C		intron	N/A	NP_066272.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDLIM1	ENST00000329399.7	TSL:1 MANE Select	c.685+117A>C		intron	N/A	ENSP00000360305.3
	PDLIM1	ENST00000477757.5	TSL:2	n.630+117A>C		intron	N/A
	PDLIM1	ENST00000490391.1	TSL:2	n.406+117A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0829 AC: 12611 AN: 152100 Hom.: 684 Cov.: 33

Gnomad AFR AF: 0.0213

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0990

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0408

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.0988 AC: 68269 AN: 690676 Hom.: 3976 AF XY: 0.0978 AC XY: 35062 AN XY: 358386

African (AFR) AF: 0.0191 AC: 330 AN: 17286

American (AMR) AF: 0.0746 AC: 1922 AN: 25780

Ashkenazi Jewish (ASJ) AF: 0.0967 AC: 1511 AN: 15628

East Asian (EAS) AF: 0.0000860 AC: 3 AN: 34872

South Asian (SAS) AF: 0.0453 AC: 2220 AN: 49012

European-Finnish (FIN) AF: 0.116 AC: 4825 AN: 41668

Middle Eastern (MID) AF: 0.145 AC: 567 AN: 3908

European-Non Finnish (NFE) AF: 0.114 AC: 53613 AN: 468414

Other (OTH) AF: 0.0961 AC: 3278 AN: 34108

GnomAD4 genome AF: 0.0828 AC: 12603 AN: 152218 Hom.: 684 Cov.: 33 AF XY: 0.0823 AC XY: 6127 AN XY: 74424

African (AFR) AF: 0.0212 AC: 881 AN: 41544

American (AMR) AF: 0.0988 AC: 1509 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 355 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5192

South Asian (SAS) AF: 0.0406 AC: 196 AN: 4830

European-Finnish (FIN) AF: 0.123 AC: 1299 AN: 10596

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.117 AC: 7978 AN: 67994

Other (OTH) AF: 0.103 AC: 217 AN: 2114

Alfa AF: 0.0854 Hom.: 93

Bravo AF: 0.0803

Asia WGS AF: 0.0200 AC: 74 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.56
PhyloP100		-0.26
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: rs17525659; hg19: chr10-97006855;