chr4-185502168-GTCTAAAGCCTTGACTTTAGATTTGGAGTTGACAA-G

Position:

• chr4-185502168-GTCTAAAGCCTTGACTTTAGATTTGGAGTTGACAA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014476.6(PDLIM3):​c.*92_*125del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00757 in 971,948 control chromosomes in the GnomAD database, including 305 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (177 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (128 hom.)
• Consequence: PDLIM3 NM_014476.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.52

Genes affected

PDLIM3 (HGNC:20767): (PDZ and LIM domain 3) The protein encoded by this gene contains a PDZ domain and a LIM domain, indicating that it may be involved in cytoskeletal assembly. In support of this, the encoded protein has been shown to bind the spectrin-like repeats of alpha-actinin-2 and to colocalize with alpha-actinin-2 at the Z lines of skeletal muscle. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. Aberrant alternative splicing of this gene may play a role in myotonic dystrophy. [provided by RefSeq, Apr 2012]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 4-185502168-GTCTAAAGCCTTGACTTTAGATTTGGAGTTGACAA-G is Benign according to our data. Variant chr4-185502168-GTCTAAAGCCTTGACTTTAGATTTGGAGTTGACAA-G is described in ClinVar as [Benign]. Clinvar id is 1230235.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDLIM3	NM_014476.6	c.*92_*125del		3_prime_UTR_variant	8/8	ENST00000284767.12	NP_055291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDLIM3	ENST00000284767.12	c.*92_*125del		3_prime_UTR_variant	8/8	5	NM_014476.6	ENSP00000284767	A1
	ENST00000671042.1	n.518-4329_518-4296del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3989 AN: 152138 Hom.: 176 Cov.: 32

Gnomad AFR AF: 0.0907

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0201

GnomAD4 exome AF: 0.00410 AC: 3357 AN: 819692 Hom.: 128 AF XY: 0.00325 AC XY: 1399 AN XY: 430644

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.00555

Gnomad4 ASJ exome AF: 0.000183

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000227

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000160

Gnomad4 OTH exome AF: 0.00828

GnomAD4 genome AF: 0.0262 AC: 3996 AN: 152256 Hom.: 177 Cov.: 32 AF XY: 0.0254 AC XY: 1893 AN XY: 74438

Gnomad4 AFR AF: 0.0906

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000382

Gnomad4 OTH AF: 0.0198

Alfa AF: 0.0231 Hom.: 17

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 06, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs138685478; hg19: chr4-186423322;