Variant 8-84529428-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000521268.6(RALYL):c.107T>C(p.Val36Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,613,316 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00057 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 1 hom. )

Consequence

RALYL
ENST00000521268.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.33

Variant links:

Genes affected

RALYL (HGNC:27036): (RALY RNA binding protein like) Enables identical protein binding activity. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RALYL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.036596775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RALYL	NM_173848.7 linkuse as main transcript	c.107T>C	p.Val36Ala	missense_variant	2/9	ENST00000521268.6	NP_776247.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RALYL	ENST00000521268.6 linkuse as main transcript	c.107T>C	p.Val36Ala	missense_variant	2/9	1	NM_173848.7	ENSP00000430367	P1	Q86SE5-1

Frequencies

GnomAD3 genomes

AF:

0.000572

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

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:

0.00103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000451

AC:

112

AN:

248126

Hom.:

AF XY:

0.000460

AC XY:

AN XY:

134638

show subpopulations

Gnomad AFR exome

AF:

0.000326

Gnomad AMR exome

AF:

0.000117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000656

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000888

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.00113

AC:

1644

AN:

1461160

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

771

AN XY:

726812

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00142

Gnomad4 OTH exome

AF:

0.000812

GnomAD4 genome

AF:

0.000572

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000499

Hom.:

Bravo

AF:

0.000642

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000507

AC:

ESP6500EA

AF:

0.000839

AC:

ExAC

AF:

0.000372

AC:

EpiCase

AF:

0.00115

EpiControl

AF:

0.00119

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

Dec 31, 2023

The c.146T>C (p.V49A) alteration is located in exon 2 (coding exon 2) of the RALYL gene. This alteration results from a T to C substitution at nucleotide position 146, causing the valine (V) at amino acid position 49 to be replaced by an alanine (A). 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

0.066

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0026

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

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.39

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.80

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

M_CAP

Benign

0.0028

MetaRNN

Benign

0.037

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.65

.;N;N;N;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.70

PROVEAN

Benign

1.6

N;N;N;N;N;N;N;N

REVEL

Benign

0.049

Sift

Benign

0.32

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

Sift4G

Benign

0.47

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

Polyphen

0.0

.;B;B;B;B;.;.;.

Vest4

0.083, 0.084, 0.10, 0.12

MVP

0.24

MPC

1.1

ClinPred

0.012

GERP RS

0.98

Varity_R

0.046

gMVP

0.44

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