Variant 8-94378629-C-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_012415.3(RAD54B):c.2253G>T(p.Met751Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000505 in 1,604,268 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

RAD54B
NM_012415.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.70

Variant links:

Genes affected

RAD54B (HGNC:17228): (RAD54 homolog B) The protein encoded by this gene belongs to the DEAD-like helicase superfamily. It shares similarity with Saccharomyces cerevisiae RAD54 and RDH54, both of which are involved in homologous recombination and repair of DNA. This protein binds to double-stranded DNA, and displays ATPase activity in the presence of DNA. This gene is highly expressed in testis and spleen, which suggests active roles in meiotic and mitotic recombination. Homozygous mutations of this gene were observed in primary lymphoma and colon cancer. [provided by RefSeq, Jul 2008]

RAD54B links:

FSBP (HGNC:43653): (fibrinogen silencer binding protein) Enables identical protein binding activity. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FSBP 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
RAD54B	NM_012415.3 linkuse as main transcript	c.2253G>T	p.Met751Ile	missense_variant	13/15	ENST00000336148.10	NP_036547.1	Q9Y620-1
RAD54B	NM_001205263.2 linkuse as main transcript	c.1701G>T	p.Met567Ile	missense_variant	11/13		NP_001192192.1	Q9Y620

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RAD54B	ENST00000336148.10 linkuse as main transcript	c.2253G>T	p.Met751Ile	missense_variant	13/15	1	NM_012415.3	ENSP00000336606.5	Q9Y620-1
FSBP	ENST00000517506.2 linkuse as main transcript	n.*1933G>T		non_coding_transcript_exon_variant	11/12	5		ENSP00000462684.1	J3KSW4
FSBP	ENST00000517506.2 linkuse as main transcript	n.*1933G>T		3_prime_UTR_variant	11/12	5		ENSP00000462684.1	J3KSW4

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000527

AC:

AN:

246510

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

133098

show subpopulations

Gnomad AFR exome

AF:

0.000619

Gnomad AMR exome

AF:

0.0000900

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000351

AC:

AN:

1451948

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

722640

show subpopulations

Gnomad4 AFR exome

AF:

0.00124

Gnomad4 AMR exome

AF:

0.0000688

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:

9.04e-7

Gnomad4 OTH exome

AF:

0.0000999

GnomAD4 genome

AF:

0.000197

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000194

Hom.:

Bravo

AF:

0.000242

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

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

Dec 05, 2024

The c.2253G>T (p.M751I) alteration is located in exon 13 (coding exon 12) of the RAD54B gene. This alteration results from a G to T substitution at nucleotide position 2253, causing the methionine (M) at amino acid position 751 to be replaced by an isoleucine (I). 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

Pathogenic

0.75

BayesDel_addAF

Benign

-0.025

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

D;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;D

M_CAP

Benign

0.055

MetaRNN

Uncertain

0.68

D;D

MetaSVM

Benign

-0.29

MutationAssessor

Benign

1.1

L;.

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.7

D;.

REVEL

Uncertain

0.54

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.062

T;D

Polyphen

1.0

D;.

Vest4

0.84

MutPred

0.48

Loss of MoRF binding (P = 0.1022);.;

MVP

0.88

MPC

0.48

ClinPred

0.74

GERP RS

3.9

Varity_R

0.81

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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