chr19-55762006-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001145014.2(RFPL4A):​c.206C>T​(p.Ala69Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000273 in 146,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 30)
Exomes 𝑓: 0.00020 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RFPL4A
NM_001145014.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.10
Variant links:
Genes affected
RFPL4A (HGNC:16449): (ret finger protein like 4A) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in positive regulation of transcription, DNA-templated. Predicted to be located in nucleus. Predicted to be active in chromatin and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.016938537).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RFPL4ANM_001145014.2 linkc.206C>T p.Ala69Val missense_variant Exon 2 of 3 ENST00000434937.3 NP_001138486.1 A6NLU0
RFPL4AXM_011526915.4 linkc.377C>T p.Ala126Val missense_variant Exon 3 of 4 XP_011525217.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RFPL4AENST00000434937.3 linkc.206C>T p.Ala69Val missense_variant Exon 2 of 3 5 NM_001145014.2 ENSP00000392936.2 A6NLU0

Frequencies

GnomAD3 genomes
AF:
0.000273
AC:
40
AN:
146336
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.000470
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000676
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000216
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000271
Gnomad OTH
AF:
0.000993
GnomAD3 exomes
AF:
0.000212
AC:
32
AN:
150640
Hom.:
0
AF XY:
0.000225
AC XY:
18
AN XY:
79946
show subpopulations
Gnomad AFR exome
AF:
0.000688
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000894
Gnomad SAS exome
AF:
0.000232
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000363
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000195
AC:
266
AN:
1363472
Hom.:
0
Cov.:
34
AF XY:
0.000201
AC XY:
135
AN XY:
672694
show subpopulations
Gnomad4 AFR exome
AF:
0.000300
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000558
Gnomad4 SAS exome
AF:
0.000154
Gnomad4 FIN exome
AF:
0.0000204
Gnomad4 NFE exome
AF:
0.000220
Gnomad4 OTH exome
AF:
0.000194
GnomAD4 genome
AF:
0.000273
AC:
40
AN:
146446
Hom.:
0
Cov.:
30
AF XY:
0.000294
AC XY:
21
AN XY:
71516
show subpopulations
Gnomad4 AFR
AF:
0.000468
Gnomad4 AMR
AF:
0.0000675
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000216
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000271
Gnomad4 OTH
AF:
0.000982
Alfa
AF:
0.000158
Hom.:
0
ExAC
AF:
0.000175
AC:
17

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 08, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.206C>T (p.A69V) alteration is located in exon 2 (coding exon 1) of the RFPL4A gene. This alteration results from a C to T substitution at nucleotide position 206, causing the alanine (A) at amino acid position 69 to be replaced by a valine (V). 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
Benign
0.13
BayesDel_addAF
Benign
-0.65
T
BayesDel_noAF
Benign
-0.79
CADD
Benign
3.7
DANN
Benign
0.70
DEOGEN2
Benign
0.021
T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.0023
N
LIST_S2
Benign
0.26
T
M_CAP
Benign
0.0017
T
MetaRNN
Benign
0.017
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
L
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.014
Sift
Benign
0.32
T
Sift4G
Benign
0.30
T
Polyphen
0.33
B
Vest4
0.028
MVP
0.014
MPC
0.82
ClinPred
0.0053
T
GERP RS
-6.6
Varity_R
0.034
gMVP
0.061

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: rs528943290; hg19: chr19-56273372; API