Variant 5-34757524-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_015577.3(RAI14):c.93T>G(p.Asp31Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000512 in 1,613,970 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00029 ( 1 hom. )

Consequence

RAI14
NM_015577.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.144

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0054365396).

BP6

Variant 5-34757524-T-G is Benign according to our data. Variant chr5-34757524-T-G is described in ClinVar as [Benign]. Clinvar id is 773931.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAI14	NM_015577.3 link	c.93T>G	p.Asp31Glu	missense_variant	3/18	ENST00000265109.8	NP_056392.2	Q9P0K7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAI14	ENST00000265109.8 link	c.93T>G	p.Asp31Glu	missense_variant	3/18	1	NM_015577.3	ENSP00000265109.3		Q9P0K7-1

Frequencies

GnomAD3 genomes

AF:

0.00265

AC:

404

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000685

AC:

172

AN:

251224

Hom.:

AF XY:

0.000523

AC XY:

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.00867

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000290

AC:

424

AN:

1461678

Hom.:

Cov.:

AF XY:

0.000250

AC XY:

182

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.00929

Gnomad4 AMR exome

AF:

0.000559

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.000679

GnomAD4 genome

AF:

0.00265

AC:

403

AN:

152292

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

203

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00912

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000415

Hom.:

Bravo

AF:

0.00284

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0104

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000947

AC:

115

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 06, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Benign

0.83

DANN

Benign

0.94

DEOGEN2

Benign

0.19

T;T;.;.;T;.;T;T;T;T;.;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.16

LIST_S2

Uncertain

0.94

.;D;.;D;.;D;D;D;D;D;D;D;D;D

MetaRNN

Benign

0.0054

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.14

PrimateAI

Benign

0.48

PROVEAN

Benign

-2.0

N;D;D;N;N;D;N;N;N;N;N;D;D;N

REVEL

Uncertain

0.30

Sift

Benign

0.28

T;T;T;T;T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.37

T;T;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

1.0

D;.;.;.;D;.;D;.;.;.;P;.;.;P

Vest4

0.14

MutPred

0.34

Gain of ubiquitination at K34 (P = 0.1418);Gain of ubiquitination at K34 (P = 0.1418);Gain of ubiquitination at K34 (P = 0.1418);Gain of ubiquitination at K34 (P = 0.1418);Gain of ubiquitination at K34 (P = 0.1418);Gain of ubiquitination at K34 (P = 0.1418);Gain of ubiquitination at K34 (P = 0.1418);Gain of ubiquitination at K34 (P = 0.1418);Gain of ubiquitination at K34 (P = 0.1418);Gain of ubiquitination at K34 (P = 0.1418);.;Gain of ubiquitination at K34 (P = 0.1418);Gain of ubiquitination at K34 (P = 0.1418);.;

MVP

0.44

MPC

0.65

ClinPred

0.026

GERP RS

-11

Varity_R

0.071

gMVP

0.16

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.

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