rs116676966

Variant names:

• chr4-94575680-C-G
• rs116676966
• NM_006457.5:c.356C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-94575680-C-G
• chr4-94575680-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001256428.2(PDLIM5):​c.-11C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000534 in 1,612,808 control chromosomes in the GnomAD database, including 5 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 0.0029 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (5 hom.)
• Consequence: PDLIM5 NM_001256428.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.81
• Publications: 0 publications found

Genes affected

PDLIM5 (HGNC:17468): (PDZ and LIM domain 5) This gene encodes a member of a family of proteins that possess a 100-amino acid PDZ domain at the N terminus and one to three LIM domains at the C-terminus. This family member functions as a scaffold protein that tethers protein kinases to the Z-disk in striated muscles. It is thought to function in cardiomyocyte expansion and in restraining postsynaptic growth of excitatory synapses. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2012]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007248968).
• BS2: High AC in GnomAd4 at 441 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256428.2. 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
	PDLIM5	NM_006457.5	MANE Select	c.356C>G	p.Ser119Cys	missense	Exon 5 of 13	NP_006448.5	Q96HC4-1
	PDLIM5	NM_001256428.2		c.-11C>G		5_prime_UTR_premature_start_codon_gain	Exon 4 of 12	NP_001243357.2
	PDLIM5	NM_001256428.2		c.-11C>G		5_prime_UTR	Exon 4 of 12	NP_001243357.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDLIM5	ENST00000317968.9	TSL:1 MANE Select	c.356C>G	p.Ser119Cys	missense	Exon 5 of 13	ENSP00000321746.4	Q96HC4-1
	PDLIM5	ENST00000615540.4	TSL:1	c.292-263C>G		intron	N/A	ENSP00000480359.1	Q96HC4-6
	PDLIM5	ENST00000542407.5	TSL:1	c.292-263C>G		intron	N/A	ENSP00000442187.2	Q96HC4-4

Frequencies

GnomAD3 genomes AF: 0.00290 AC: 442 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.000631 AC: 158 AN: 250230 AF XY: 0.000436

Gnomad AFR exome AF: 0.00904

Gnomad AMR exome AF: 0.000260

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: 0.000328

GnomAD4 exome AF: 0.000288 AC: 420 AN: 1460516 Hom.: 5 Cov.: 31 AF XY: 0.000226 AC XY: 164 AN XY: 726542

African (AFR) AF: 0.0109 AC: 366 AN: 33476

American (AMR) AF: 0.000336 AC: 15 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26004

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86080

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53318

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5762

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111144

Other (OTH) AF: 0.000580 AC: 35 AN: 60354

GnomAD4 genome AF: 0.00290 AC: 441 AN: 152292 Hom.: 0 Cov.: 32 AF XY: 0.00265 AC XY: 197 AN XY: 74468

African (AFR) AF: 0.0102 AC: 422 AN: 41570

American (AMR) AF: 0.000719 AC: 11 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.000805 Hom.: 0

Bravo AF: 0.00317

ESP6500AA AF: 0.00908 AC: 40

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000857 AC: 104

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.82	T
MetaRNN	Benign	0.0072	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.8
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.094
Sift	Benign	0.080	T
Sift4G	Benign	0.068	T
Polyphen		0.99	D
Vest4		0.27
MVP		0.71
ClinPred		0.030	T
GERP RS		5.3
Varity_R		0.16
Mutation Taster		=291/9	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: rs116676966; hg19: chr4-95496831;