Variant 20-34075911-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_016732.3(RALY):c.415G>A(p.Val139Met) variant causes a missense change. The variant allele was found at a frequency of 0.0013 in 1,614,062 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0070 ( 13 hom., cov: 32)

Exomes 𝑓: 0.00071 ( 13 hom. )

Consequence

RALY
NM_016732.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.01

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007173568).

BP6

Variant 20-34075911-G-A is Benign according to our data. Variant chr20-34075911-G-A is described in ClinVar as [Benign]. Clinvar id is 786970.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00697 (1061/152304) while in subpopulation AFR AF= 0.0236 (982/41572). AF 95% confidence interval is 0.0224. There are 13 homozygotes in gnomad4. There are 497 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RALY	NM_016732.3 linkuse as main transcript	c.415G>A	p.Val139Met	missense_variant	6/10	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.415G>A	p.Val139Met	missense_variant	6/10	1	NM_016732.3	ENSP00000246194	P3	Q9UKM9-1

Frequencies

GnomAD3 genomes

AF:

0.00697

AC:

1060

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0237

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00406

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:

0.0000735

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00164

AC:

411

AN:

250868

Hom.:

AF XY:

0.00114

AC XY:

154

AN XY:

135670

show subpopulations

Gnomad AFR exome

AF:

0.0223

Gnomad AMR exome

AF:

0.00116

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:

0.0000265

Gnomad OTH exome

AF:

0.000980

GnomAD4 exome

AF:

0.000705

AC:

1031

AN:

1461758

Hom.:

Cov.:

AF XY:

0.000606

AC XY:

441

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.0246

Gnomad4 AMR exome

AF:

0.00141

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:

0.0000252

Gnomad4 OTH exome

AF:

0.00177

GnomAD4 genome

AF:

0.00697

AC:

1061

AN:

152304

Hom.:

Cov.:

AF XY:

0.00667

AC XY:

497

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0236

Gnomad4 AMR

AF:

0.00405

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00123

Hom.:

Bravo

AF:

0.00820

ESP6500AA

AF:

0.0225

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00205

AC:

249

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0000545

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	May 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

.;T;T;T;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.94

D;D;D;D;D

MetaRNN

Benign

0.0072

T;T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.1

.;.;M;.;.

MutationTaster

Benign

0.98

D;D

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.51

N;N;N;N;N

REVEL

Benign

0.15

Sift

Uncertain

0.0080

D;D;D;T;T

Sift4G

Benign

0.17

T;T;T;T;T

Polyphen

0.99

D;.;D;.;.

Vest4

0.54

MVP

0.31

MPC

1.4

ClinPred

0.023

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.051

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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