Variant 8-84862382-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173848.7(RALYL):c.500G>A(p.Arg167His) variant causes a missense change. The variant allele was found at a frequency of 0.0000796 in 1,607,200 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000080 ( 0 hom. )

Consequence

RALYL
NM_173848.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.15

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RALYL	NM_173848.7 link	c.500G>A	p.Arg167His	missense_variant	6/9	ENST00000521268.6	NP_776247.3	Q86SE5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RALYL	ENST00000521268.6 link	c.500G>A	p.Arg167His	missense_variant	6/9	1	NM_173848.7	ENSP00000430367.1		Q86SE5-1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000373

AC:

AN:

241292

Hom.:

AF XY:

0.0000305

AC XY:

AN XY:

131120

show subpopulations

Gnomad AFR exome

AF:

0.0000676

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000234

Gnomad SAS exome

AF:

0.0000340

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000272

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000804

AC:

117

AN:

1454924

Hom.:

Cov.:

AF XY:

0.0000663

AC XY:

AN XY:

723654

show subpopulations

Gnomad4 AFR exome

AF:

0.0000910

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00177

Gnomad4 SAS exome

AF:

0.0000587

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000334

Gnomad4 OTH exome

AF:

0.0000499

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000676

Hom.:

Bravo

AF:

0.0000529

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000248

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

May 04, 2023

The c.539G>A (p.R180H) alteration is located in exon 6 (coding exon 6) of the RALYL gene. This alteration results from a G to A substitution at nucleotide position 539, causing the arginine (R) at amino acid position 180 to be replaced by a histidine (H). 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

0.38

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.18

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

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.87

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

M_CAP

Benign

0.046

MetaRNN

Uncertain

0.47

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

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.1

M;M;M;.;.;.;.

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-2.9

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

REVEL

Benign

0.20

Sift

Uncertain

0.014

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

Sift4G

Uncertain

0.052

T;T;T;T;D;D;T

Polyphen

0.99

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

Vest4

0.74

MVP

0.63

MPC

0.060

ClinPred

0.64

GERP RS

5.1

Varity_R

0.37

gMVP

0.43

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