Variant chr20-34077108-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016732.3(RALY):c.739G>A(p.Gly247Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,599,086 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: 𝑓 0.000099 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

RALY
NM_016732.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.382

Variant links:

Genes affected

RALY (HGNC:15921): (RALY heterogeneous nuclear ribonucleoprotein) This gene encodes a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) gene family. This protein may play a role in pre-mRNA splicing and in embryonic development. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

RALY 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=0.046438605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RALY	NM_016732.3 linkuse as main transcript	c.739G>A	p.Gly247Ser	missense_variant	8/10	ENST00000246194.8	NP_057951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RALY	ENST00000246194.8 linkuse as main transcript	c.739G>A	p.Gly247Ser	missense_variant	8/10	1	NM_016732.3	ENSP00000246194	P3	Q9UKM9-1

Frequencies

GnomAD3 genomes

AF:

0.0000987

AC:

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000815

AC:

AN:

220756

Hom.:

AF XY:

0.0000410

AC XY:

AN XY:

121872

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:

0.000181

Gnomad OTH exome

AF:

0.000184

GnomAD4 exome

AF:

0.000149

AC:

216

AN:

1446952

Hom.:

Cov.:

AF XY:

0.000143

AC XY:

103

AN XY:

718964

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:

0.0000196

Gnomad4 NFE exome

AF:

0.000192

Gnomad4 OTH exome

AF:

0.0000504

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000143

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000252

AC:

ExAC

AF:

0.0000876

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

Jun 09, 2022

The c.739G>A (p.G247S) alteration is located in exon 1 (coding exon 1) of the RALY gene. This alteration results from a G to A substitution at nucleotide position 739, causing the glycine (G) at amino acid position 247 to be replaced by a serine (S). 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

0.084

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.31

CADD

Benign

4.6

DANN

Benign

0.77

DEOGEN2

Benign

0.066

.;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.69

T;T;T

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.046

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.20

.;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.68

PROVEAN

Benign

0.32

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.18

T;T;T

Sift4G

Benign

0.075

T;D;D

Polyphen

0.0010

B;B;.

Vest4

0.30

MVP

0.74

MPC

0.53

ClinPred

0.024

GERP RS

0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.041

gMVP

0.28

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