Variant 5-34811076-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_015577.3(RAI14):c.515T>A(p.Leu172Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000026 in 1,614,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

RAI14
NM_015577.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.74

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]

RAI14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.952

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAI14	NM_015577.3 linkuse as main transcript	c.515T>A	p.Leu172Gln	missense_variant	8/18	ENST00000265109.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAI14	ENST00000265109.8 linkuse as main transcript	c.515T>A	p.Leu172Gln	missense_variant	8/18	1	NM_015577.3	P3	Q9P0K7-1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251224

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135772

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:

0.0000219

AC:

AN:

1461848

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.0000198

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.000170

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 submitter

clinical testing

Ambry Genetics

Nov 21, 2023

The c.524T>A (p.L175Q) alteration is located in exon 10 (coding exon 7) of the RAI14 gene. This alteration results from a T to A substitution at nucleotide position 524, causing the leucine (L) at amino acid position 175 to be replaced by a glutamine (Q). 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

0.55

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.29

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.21

T;.;T;T;.;.

Eigen

Pathogenic

0.97

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Uncertain

0.87

M_CAP

Pathogenic

0.30

MetaRNN

Pathogenic

0.95

D;D;D;D;D;D

MetaSVM

Pathogenic

0.83

MutationAssessor

Uncertain

2.7

M;M;M;M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-5.4

D;D;D;D;D;D

REVEL

Pathogenic

0.86

Sift

Uncertain

0.0010

D;D;D;D;D;D

Sift4G

Uncertain

0.0040

D;D;D;D;D;D

Polyphen

1.0

D;.;D;D;D;D

Vest4

0.93

MVP

0.95

MPC

0.69

ClinPred

0.98

GERP RS

5.7

Varity_R

0.87

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over