1-113766285-T-C

Position:

• chr1-113766285-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018364.5(RSBN1):​c.2104A>G​(p.Lys702Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K702R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RSBN1 NM_018364.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.30

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2641787).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSBN1	NM_018364.5	c.2104A>G	p.Lys702Glu	missense_variant	7/7	ENST00000261441.9	NP_060834.2
RSBN1	NR_130896.2	n.2286A>G		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSBN1	ENST00000261441.9	c.2104A>G	p.Lys702Glu	missense_variant	7/7	2	NM_018364.5	ENSP00000261441.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2024

The c.2104A>G (p.K702E) alteration is located in exon 7 (coding exon 7) of the RSBN1 gene. This alteration results from a A to G substitution at nucleotide position 2104, causing the lysine (K) at amino acid position 702 to be replaced by a glutamic acid (E). 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	0.39
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T;T;T;.
Eigen	Benign	-0.012
Eigen_PC	Benign	0.090
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	.;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.0	M;M;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.0	D;.;.;.
REVEL	Benign	0.26
Sift	Uncertain	0.0020	D;.;.;.
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		0.14	B;B;.;.
Vest4		0.51
MutPred		0.48		Loss of methylation at K702 (P = 0.0047);Loss of methylation at K702 (P = 0.0047);.;.;
MVP		0.13
MPC		2.6
ClinPred		0.94	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.71
gMVP		0.73

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.

Other links and lift over

hg19: chr1-114308907;