3-40462029-A-ACTGCTGCTGCTGCTGCTG

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BA1

The NM_001034996.3(RPL14):c.460_477dup(p.Ala154_Ala159dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.052 (240 hom., cov: 0)
  • Exomes 𝑓: 0.056 (2527 hom.)
  • Failed GnomAD Quality Control
• Consequence: RPL14 NM_001034996.3 inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

Genes affected

RPL14 (HGNC:10305): (ribosomal protein L14) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L14E family of ribosomal proteins. It contains a basic region-leucine zipper (bZIP)-like domain. The protein is located in the cytoplasm. This gene contains a trinucleotide (GCT) repeat tract whose length is highly polymorphic; these triplet repeats result in a stretch of alanine residues in the encoded protein. Transcript variants utilizing alternative polyA signals and alternative 5'-terminal exons exist but all encode the same protein. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001034996.3
• BP6: Variant 3-40462029-A-ACTGCTGCTGCTGCTGCTG is Benign according to our data. Variant chr3-40462029-A-ACTGCTGCTGCTGCTGCTG is described in ClinVar as [Benign]. Clinvar id is 770140.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL14	NM_001034996.3	c.460_477dup	p.Ala154_Ala159dup	inframe_insertion	6/6	ENST00000396203.7
RPL14	NM_003973.5	c.460_477dup	p.Ala154_Ala159dup	inframe_insertion	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL14	ENST00000396203.7	c.460_477dup	p.Ala154_Ala159dup	inframe_insertion	6/6	1	NM_001034996.3	P1

Frequencies

GnomAD3 genomes AF: 0.0519 AC: 7690 AN: 148278 Hom.: 241 Cov.: 0

Gnomad AFR AF: 0.0326

Gnomad AMI AF: 0.00991

Gnomad AMR AF: 0.0448

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.0267

Gnomad SAS AF: 0.0280

Gnomad FIN AF: 0.0625

Gnomad MID AF: 0.0226

Gnomad NFE AF: 0.0674

Gnomad OTH AF: 0.0472

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0563 AC: 78809 AN: 1398724 Hom.: 2527 Cov.: 80 AF XY: 0.0561 AC XY: 38942 AN XY: 694454

Gnomad4 AFR exome AF: 0.0276

Gnomad4 AMR exome AF: 0.0410

Gnomad4 ASJ exome AF: 0.0565

Gnomad4 EAS exome AF: 0.0219

Gnomad4 SAS exome AF: 0.0248

Gnomad4 FIN exome AF: 0.0644

Gnomad4 NFE exome AF: 0.0615

Gnomad4 OTH exome AF: 0.0506

GnomAD4 genome AF: 0.0518 AC: 7685 AN: 148386 Hom.: 240 Cov.: 0 AF XY: 0.0498 AC XY: 3600 AN XY: 72280

Gnomad4 AFR AF: 0.0325

Gnomad4 AMR AF: 0.0447

Gnomad4 ASJ AF: 0.0510

Gnomad4 EAS AF: 0.0262

Gnomad4 SAS AF: 0.0278

Gnomad4 FIN AF: 0.0625

Gnomad4 NFE AF: 0.0674

Gnomad4 OTH AF: 0.0482

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

Invitae

Dec 31, 2019

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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: rs57354599; hg19: chr3-40503520;