Variant 8-84887630-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_173848.7(RALYL):c.712A>G(p.Ser238Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000413 in 1,451,680 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

RALYL
NM_173848.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.98

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:

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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=0.09493524).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RALYL	NM_173848.7 link	c.712A>G	p.Ser238Gly	missense_variant	8/9	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.712A>G	p.Ser238Gly	missense_variant	8/9	1	NM_173848.7	ENSP00000430367.1		Q86SE5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000122

AC:

AN:

245112

Hom.:

AF XY:

0.00000752

AC XY:

AN XY:

132912

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:

0.0000270

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000413

AC:

AN:

1451680

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

722068

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000542

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000248

AC:

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

Jan 26, 2022

The c.751A>G (p.S251G) alteration is located in exon 8 (coding exon 8) of the RALYL gene. This alteration results from a A to G substitution at nucleotide position 751, causing the serine (S) at amino acid position 251 to be replaced by a glycine (G). 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

0.067

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.030

T;T;T;.;.;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.030

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.83

.;.;T;T;T;T

M_CAP

Benign

0.0057

MetaRNN

Benign

0.095

T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.34

N;N;N;.;.;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.96

N;N;N;N;N;N

REVEL

Benign

0.025

Sift

Benign

0.090

T;T;T;T;T;T

Sift4G

Benign

0.18

T;T;T;T;T;T

Polyphen

0.0020

B;B;B;B;.;B

Vest4

0.28

MutPred

0.24

Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);.;.;.;

MVP

0.47

MPC

0.022

ClinPred

0.24

GERP RS

5.3

Varity_R

0.078

gMVP

0.046

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