NM_144979.5:c.29A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144979.5(RBM46):​c.29A>T​(p.Asn10Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RBM46
NM_144979.5 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.56
Variant links:
Genes affected
RBM46 (HGNC:28401): (RNA binding motif protein 46) Predicted to enable mRNA binding activity. Predicted to act upstream of or within mRNA stabilization and trophectodermal cell differentiation. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.24487048).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RBM46NM_144979.5 linkc.29A>T p.Asn10Ile missense_variant Exon 2 of 5 ENST00000281722.8 NP_659416.1 Q8TBY0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RBM46ENST00000281722.8 linkc.29A>T p.Asn10Ile missense_variant Exon 2 of 5 1 NM_144979.5 ENSP00000281722.3 Q8TBY0-1
RBM46ENST00000514866.5 linkc.29A>T p.Asn10Ile missense_variant Exon 2 of 6 2 ENSP00000424500.1 Q8TBY0-3
RBM46ENST00000510397.5 linkc.29A>T p.Asn10Ile missense_variant Exon 2 of 5 2 ENSP00000422813.1 Q8TBY0-2
RBM46ENST00000512640.1 linkc.29A>T p.Asn10Ile missense_variant Exon 2 of 3 4 ENSP00000426672.1 D6RF41

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000402
AC:
1
AN:
248794
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134404
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:
0.00000885
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459666
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
726068
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000468
Hom.:
0

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 08, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.29A>T (p.N10I) alteration is located in exon 2 (coding exon 1) of the RBM46 gene. This alteration results from a A to T substitution at nucleotide position 29, causing the asparagine (N) at amino acid position 10 to be replaced by an isoleucine (I). 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
0.095
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.049
.;T;.;T
Eigen
Benign
0.12
Eigen_PC
Uncertain
0.28
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.89
D;D;D;D
M_CAP
Benign
0.0074
T
MetaRNN
Benign
0.24
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L;L;L;.
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-1.2
N;N;N;N
REVEL
Benign
0.066
Sift
Uncertain
0.0040
D;D;D;D
Sift4G
Uncertain
0.0040
D;D;D;D
Polyphen
0.45
.;P;.;.
Vest4
0.47
MutPred
0.47
Loss of disorder (P = 0.02);Loss of disorder (P = 0.02);Loss of disorder (P = 0.02);Loss of disorder (P = 0.02);
MVP
0.35
MPC
1.9
ClinPred
0.56
D
GERP RS
5.7
Varity_R
0.24
gMVP
0.57

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: rs201983049; hg19: chr4-155717933; API