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GeneBe

5-34808622-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015577.3(RAI14):c.418G>A(p.Glu140Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000867 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000090 ( 0 hom. )

Consequence

RAI14
NM_015577.3 missense

Scores

1
10
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.55
Variant links:
Genes affected
RAI14 (HGNC:14873): (retinoic acid induced 14) Predicted to enable actin binding activity. Predicted to be involved in several processes, including apoptotic signaling pathway; regulation of NIK/NF-kappaB signaling; and spermatogenesis. Located in cytosol; fibrillar center; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.42328498).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RAI14NM_015577.3 linkuse as main transcriptc.418G>A p.Glu140Lys missense_variant 7/18 ENST00000265109.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RAI14ENST00000265109.8 linkuse as main transcriptc.418G>A p.Glu140Lys missense_variant 7/181 NM_015577.3 P3Q9P0K7-1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152158
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000517
AC:
13
AN:
251412
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135878
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:
0.0000654
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.0000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000903
AC:
132
AN:
1461852
Hom.:
0
Cov.:
31
AF XY:
0.0000921
AC XY:
67
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000103
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152158
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74316
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000847
Hom.:
0
Bravo
AF:
0.0000491
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 GeneticsNov 08, 2022The c.427G>A (p.E143K) alteration is located in exon 9 (coding exon 6) of the RAI14 gene. This alteration results from a G to A substitution at nucleotide position 427, causing the glutamic acid (E) at amino acid position 143 to be replaced by a lysine (K). 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
0.15
BayesDel_addAF
Benign
-0.021
T
BayesDel_noAF
Uncertain
-0.060
Cadd
Pathogenic
26
Dann
Pathogenic
1.0
DEOGEN2
Benign
0.13
T;.;T;T;.;.;.
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Uncertain
0.94
D
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.42
T;T;T;T;T;T;T
MetaSVM
Uncertain
-0.23
T
MutationAssessor
Benign
0.84
L;L;L;L;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Uncertain
0.71
T
PROVEAN
Uncertain
-2.7
D;D;D;D;D;D;D
REVEL
Uncertain
0.31
Sift
Uncertain
0.0090
D;D;D;D;D;D;D
Sift4G
Benign
0.083
T;T;T;T;T;T;T
Polyphen
0.97
D;.;D;D;P;.;D
Vest4
0.57
MVP
0.70
MPC
0.55
ClinPred
0.45
T
GERP RS
5.5
Varity_R
0.25
gMVP
0.31

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs201315302; hg19: chr5-34808727; COSMIC: COSV54288674; COSMIC: COSV54288674; API