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GeneBe

5-34822985-C-A

Variant summary

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

The NM_015577.3(RAI14):c.1143C>A(p.Asp381Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,486 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: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

RAI14
NM_015577.3 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.961
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.087185204).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RAI14NM_015577.3 linkuse as main transcriptc.1143C>A p.Asp381Glu missense_variant 15/18 ENST00000265109.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RAI14ENST00000265109.8 linkuse as main transcriptc.1143C>A p.Asp381Glu missense_variant 15/181 NM_015577.3 P3Q9P0K7-1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
151956
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000193
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
250782
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135528
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.0000581
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461412
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
726990
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.0000448
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152074
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.000193
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000756
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000412
AC:
5

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 GeneticsMar 29, 2023The c.1152C>A (p.D384E) alteration is located in exon 17 (coding exon 14) of the RAI14 gene. This alteration results from a C to A substitution at nucleotide position 1152, causing the aspartic acid (D) at amino acid position 384 to be replaced by a glutamic acid (E). 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
0.14
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.36
Cadd
Benign
17
Dann
Uncertain
0.99
DEOGEN2
Benign
0.0091
T;.;T;T;.;.
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.22
FATHMM_MKL
Uncertain
0.91
D
M_CAP
Benign
0.0096
T
MetaRNN
Benign
0.087
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
L;.;L;L;.;.
MutationTaster
Benign
0.77
D;D;D;D;D;D;D
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-0.010
N;N;N;N;N;N
REVEL
Benign
0.12
Sift
Uncertain
0.0070
D;D;D;D;D;D
Sift4G
Benign
0.56
T;T;T;T;T;T
Polyphen
0.32
B;.;B;B;P;P
Vest4
0.41
MutPred
0.22
Gain of methylation at K376 (P = 0.1626);.;Gain of methylation at K376 (P = 0.1626);Gain of methylation at K376 (P = 0.1626);.;.;
MVP
0.30
MPC
0.39
ClinPred
0.082
T
GERP RS
2.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.087
gMVP
0.14

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: rs377452240; hg19: chr5-34823090; API