rs137902549

Variant names:

• chr10-95263883-C-A
• rs137902549
• NM_020992.4:c.514G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-95263883-C-A
• chr10-95263883-C-G
• chr10-95263883-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020992.4(PDLIM1):​c.514G>T​(p.Val172Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,290 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V172M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDLIM1 NM_020992.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03199798).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDLIM1	NM_020992.4	c.514G>T	p.Val172Leu	missense_variant	Exon 4 of 7	ENST00000329399.7	NP_066272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDLIM1	ENST00000329399.7	c.514G>T	p.Val172Leu	missense_variant	Exon 4 of 7	1	NM_020992.4	ENSP00000360305.3
PDLIM1	ENST00000477757.5	n.459G>T		non_coding_transcript_exon_variant	Exon 3 of 6	2
PDLIM1	ENST00000493949.1	n.788G>T		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249870 AF XY: 0.00000741

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460788 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726660

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5514

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111486

Other (OTH) AF: 0.00 AC: 0 AN: 60342

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152290 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74458

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41566

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2110

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.5
DANN	Benign	0.95
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.49	N
PhyloP100		1.5
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.068
Sift	Benign	0.38	T
Sift4G	Benign	0.44	T
Polyphen		0.0	B
Vest4		0.038
MutPred		0.17		Gain of phosphorylation at T167 (P = 0.2194);
MVP		0.30
MPC		0.19
ClinPred		0.062	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.067
gMVP		0.28
Mutation Taster		=95/5	polymorphism

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: rs137902549; hg19: chr10-97023640;