Genetic Variant NM_000967.4:c.197-5delT (chr22-39317633-CA-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_000967.4(RPL3):c.197-5delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000637 in 1,557,968 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00066 ( 0 hom. )

Consequence

RPL3
NM_000967.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.858

Publications

0 publications found

Variant links:

Genes affected

RPL3 (HGNC:10332): (ribosomal protein L3) Ribosomes, the complexes 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 L3P family of ribosomal proteins and it is located in the cytoplasm. The protein can bind to the HIV-1 TAR mRNA, and it has been suggested that the protein contributes to tat-mediated transactivation. This gene is co-transcribed with several small nucleolar RNA genes, which are located in several of this gene's introns. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. 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]

RPL3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 62 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000967.4. 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
	RPL3	NM_000967.4	MANE Select	c.197-5delT		splice_region intron	N/A	NP_000958.1	P39023
	RPL3	NM_001033853.2		c.197-5delT		splice_region intron	N/A	NP_001029025.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPL3	ENST00000216146.9	TSL:1 MANE Select	c.197-5delT	splice_region intron	N/A	ENSP00000346001.3	P39023
RPL3	ENST00000401609.5	TSL:1	c.41-5delT	splice_region intron	N/A	ENSP00000386101.1	G5E9G0
RPL3	ENST00000465618.5	TSL:1	n.857-5delT	splice_region intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000413

AC:

AN:

150218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000735

Gnomad AMI

AF:

0.00665

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000211

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000741

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000929

AC:

187

AN:

201362

AF XY:

0.000852

show subpopulations

Gnomad AFR exome

AF:

0.000490

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.000698

Gnomad EAS exome

AF:

0.000805

Gnomad FIN exome

AF:

0.0000521

Gnomad NFE exome

AF:

0.00120

Gnomad OTH exome

AF:

0.00127

GnomAD4 exome

AF:

0.000661

AC:

931

AN:

1407640

Hom.:

Cov.:

AF XY:

0.000644

AC XY:

451

AN XY:

700036

show subpopulations

African (AFR)

AF:

0.000321

AC:

AN:

31170

American (AMR)

AF:

0.000877

AC:

AN:

38750

Ashkenazi Jewish (ASJ)

AF:

0.0000814

AC:

AN:

24572

East Asian (EAS)

AF:

0.000105

AC:

AN:

38182

South Asian (SAS)

AF:

0.000470

AC:

AN:

80858

European-Finnish (FIN)

AF:

0.0000387

AC:

AN:

51690

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5510

European-Non Finnish (NFE)

AF:

0.000725

AC:

782

AN:

1079250

Other (OTH)

AF:

0.00102

AC:

AN:

57658

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

130

173

216

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000412

AC:

AN:

150328

Hom.:

Cov.:

AF XY:

0.000327

AC XY:

AN XY:

73366

show subpopulations

African (AFR)

AF:

0.0000733

AC:

AN:

40948

American (AMR)

AF:

0.000132

AC:

AN:

15118

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.000211

AC:

AN:

4736

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10136

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000741

AC:

AN:

67502

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00560

Hom.:

Bravo

AF:

0.000457

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.86

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over