2-216500018-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_000998.5(RPL37A):​c.202G>T​(p.Ala68Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,042 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000068 ( 1 hom. )

Consequence

RPL37A
NM_000998.5 missense

Scores

4
10
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.04
Variant links:
Genes affected
RPL37A (HGNC:10348): (ribosomal protein L37a) 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 L37AE family of ribosomal proteins. It is located in the cytoplasm. The protein contains a C4-type zinc finger-like domain. 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.9
BS2
High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RPL37ANM_000998.5 linkc.202G>T p.Ala68Ser missense_variant 3/4 ENST00000491306.6 NP_000989.1 P61513

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RPL37AENST00000491306.6 linkc.202G>T p.Ala68Ser missense_variant 3/41 NM_000998.5 ENSP00000418082.1 P61513

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251460
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135906
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461042
Hom.:
1
Cov.:
30
AF XY:
0.00000688
AC XY:
5
AN XY:
726832
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000720
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000264
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 22, 2023The c.202G>T (p.A68S) alteration is located in exon 3 (coding exon 3) of the RPL37A gene. This alteration results from a G to T substitution at nucleotide position 202, causing the alanine (A) at amino acid position 68 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.54
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Uncertain
0.11
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.44
T;T;.;.;T;.;.
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.86
D;D;D;D;D;.;D
M_CAP
Benign
0.065
D
MetaRNN
Pathogenic
0.90
D;D;D;D;D;D;D
MetaSVM
Benign
-0.51
T
PrimateAI
Pathogenic
0.83
D
PROVEAN
Uncertain
-2.8
D;.;D;D;.;.;.
REVEL
Uncertain
0.37
Sift
Uncertain
0.025
D;.;D;D;.;.;.
Sift4G
Uncertain
0.047
D;D;T;T;D;T;T
Polyphen
0.085
B;P;.;.;.;.;.
Vest4
0.89
MutPred
0.85
Gain of MoRF binding (P = 0.1144);Gain of MoRF binding (P = 0.1144);Gain of MoRF binding (P = 0.1144);.;.;.;.;
MVP
0.32
MPC
0.80
ClinPred
0.94
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.28
gMVP
0.59

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs745839935; hg19: chr2-217364741; API