Variant 1-113797929-G-A 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_018364.5(RSBN1):c.811C>T(p.Leu271Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RSBN1
NM_018364.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.16

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:

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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=0.20829743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RSBN1	NM_018364.5 linkuse as main transcript	c.811C>T	p.Leu271Phe	missense_variant	2/7	ENST00000261441.9
RSBN1	XM_017001518.3 linkuse as main transcript	c.811C>T	p.Leu271Phe	missense_variant	2/3
RSBN1	NR_130896.2 linkuse as main transcript	n.875C>T		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.811C>T	p.Leu271Phe	missense_variant	2/7	2	NM_018364.5	P1	Q5VWQ0-1
RSBN1	ENST00000612242.4 linkuse as main transcript	c.811C>T	p.Leu271Phe	missense_variant	2/7	2		P1	Q5VWQ0-1
RSBN1	ENST00000615321.1 linkuse as main transcript	c.667C>T	p.Leu223Phe	missense_variant	2/7	2
RSBN1	ENST00000476412.5 linkuse as main transcript	c.667C>T	p.Leu223Phe	missense_variant, NMD_transcript_variant	2/8	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461740

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727164

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 11, 2022

The c.811C>T (p.L271F) alteration is located in exon 2 (coding exon 2) of the RSBN1 gene. This alteration results from a C to T substitution at nucleotide position 811, causing the leucine (L) at amino acid position 271 to be replaced by a phenylalanine (F). 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

Uncertain

0.44

BayesDel_addAF

Benign

-0.0012

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.063

T;T;T;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

.;D;D;D

M_CAP

Benign

0.0017

MetaRNN

Benign

0.21

T;T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.4

L;L;.;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.7

N;.;.;.

REVEL

Benign

0.097

Sift

Benign

0.042

D;.;.;.

Sift4G

Benign

0.18

T;T;T;T

Polyphen

0.96

D;D;.;.

Vest4

0.29

MutPred

0.27

Gain of methylation at K272 (P = 0.031);Gain of methylation at K272 (P = 0.031);.;.;

MVP

0.043

MPC

1.1

ClinPred

0.78

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.11

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over