Variant 1-113797899-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_018364.5(RSBN1):c.841G>A(p.Val281Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000676 in 1,612,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000060 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

RSBN1
NM_018364.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.24

Variant links:

Genes affected

RSBN1 (HGNC:25642): (round spermatid basic protein 1) Predicted to enable dioxygenase activity and metal ion binding activity. Predicted to be involved in chromatin organization. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RSBN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.046406686).

BS2

High AC in GnomAd at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RSBN1	NM_018364.5 linkuse as main transcript	c.841G>A	p.Val281Ile	missense_variant	2/7	ENST00000261441.9
RSBN1	XM_017001518.3 linkuse as main transcript	c.841G>A	p.Val281Ile	missense_variant	2/3
RSBN1	NR_130896.2 linkuse as main transcript	n.905G>A		non_coding_transcript_exon_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSBN1	ENST00000261441.9 linkuse as main transcript	c.841G>A	p.Val281Ile	missense_variant	2/7	2	NM_018364.5	P1	Q5VWQ0-1
RSBN1	ENST00000612242.4 linkuse as main transcript	c.841G>A	p.Val281Ile	missense_variant	2/7	2		P1	Q5VWQ0-1
RSBN1	ENST00000615321.1 linkuse as main transcript	c.697G>A	p.Val233Ile	missense_variant	2/7	2
RSBN1	ENST00000476412.5 linkuse as main transcript	c.697G>A	p.Val233Ile	missense_variant, NMD_transcript_variant	2/8	2

Frequencies

GnomAD3 genomes

AF:

0.0000596

AC:

AN:

151040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000662

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.0000969

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000884

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000837

AC:

AN:

250956

Hom.:

AF XY:

0.0000959

AC XY:

AN XY:

135620

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000706

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000684

AC:

100

AN:

1461816

Hom.:

Cov.:

AF XY:

0.0000743

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.0000692

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.0000595

AC:

AN:

151158

Hom.:

Cov.:

AF XY:

0.0000814

AC XY:

AN XY:

73752

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000661

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.0000969

Gnomad4 NFE

AF:

0.0000884

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000184

Hom.:

Bravo

AF:

0.0000378

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Aug 09, 2021

The c.841G>A (p.V281I) alteration is located in exon 2 (coding exon 2) of the RSBN1 gene. This alteration results from a G to A substitution at nucleotide position 841, causing the valine (V) at amino acid position 281 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

Benign

0.075

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.48

Cadd

Benign

Dann

Benign

0.94

DEOGEN2

Benign

0.034

T;T;T;.

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.93

M_CAP

Benign

0.0029

MetaRNN

Benign

0.046

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L;.;.

MutationTaster

Benign

0.91

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.21

N;.;.;.

REVEL

Benign

0.021

Sift

Benign

0.33

T;.;.;.

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0030

B;B;.;.

Vest4

0.14

MutPred

0.33

Gain of methylation at K276 (P = 0.0871);Gain of methylation at K276 (P = 0.0871);.;.;

MVP

0.043

MPC

0.58

ClinPred

0.046

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.029

gMVP

0.065

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