Variant chr1-113797460-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_018364.5(RSBN1):c.1280A>G(p.Asp427Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RSBN1
NM_018364.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.02

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.744

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSBN1	NM_018364.5 link	c.1280A>G	p.Asp427Gly	missense_variant	2/7	ENST00000261441.9	NP_060834.2	Q5VWQ0-1
RSBN1	XM_017001518.3 link	c.1280A>G	p.Asp427Gly	missense_variant	2/3		XP_016857007.1	Q5VWQ0-4
RSBN1	NR_130896.2 link	n.1344A>G		non_coding_transcript_exon_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RSBN1	ENST00000261441.9 link	c.1280A>G	p.Asp427Gly	missense_variant	2/7	2	NM_018364.5	ENSP00000261441.5	Q5VWQ0-1
RSBN1	ENST00000612242.4 link	c.1280A>G	p.Asp427Gly	missense_variant	2/7	2		ENSP00000479490.1	Q5VWQ0-1
RSBN1	ENST00000615321.1 link	c.1136A>G	p.Asp379Gly	missense_variant	2/7	2		ENSP00000480408.1	A0A087WWP8
RSBN1	ENST00000476412.5 link	n.1136A>G		non_coding_transcript_exon_variant	2/8	2		ENSP00000433256.2	A0A0C4DH79

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461766

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

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

Jul 10, 2024

The c.1280A>G (p.D427G) alteration is located in exon 2 (coding exon 2) of the RSBN1 gene. This alteration results from a A to G substitution at nucleotide position 1280, causing the aspartic acid (D) at amino acid position 427 to be replaced by a glycine (G). 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

0.95

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

T;T;T;.

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

.;D;D;D

M_CAP

Benign

0.0029

MetaRNN

Pathogenic

0.74

D;D;D;D

MetaSVM

Benign

-0.49

MutationAssessor

Uncertain

2.2

M;M;.;.

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-5.8

D;.;.;.

REVEL

Uncertain

0.59

Sift

Benign

0.035

D;.;.;.

Sift4G

Uncertain

0.047

D;D;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.81

MutPred

0.54

Loss of stability (P = 0.0591);Loss of stability (P = 0.0591);.;.;

MVP

0.068

MPC

2.8

ClinPred

0.98

GERP RS

6.0

Varity_R

0.64

gMVP

0.95

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