chr1-113797560-C-T

Variant names:

• chr1-113797560-C-T
• NM_018364.5:c.1180G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018364.5(RSBN1):​c.1180G>A​(p.Glu394Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,706 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RSBN1 NM_018364.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSBN1	NM_018364.5	c.1180G>A	p.Glu394Lys	missense_variant	Exon 2 of 7	ENST00000261441.9	NP_060834.2
RSBN1	XM_017001518.3	c.1180G>A	p.Glu394Lys	missense_variant	Exon 2 of 3		XP_016857007.1
RSBN1	NR_130896.2	n.1244G>A		non_coding_transcript_exon_variant	Exon 2 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSBN1	ENST00000261441.9	c.1180G>A	p.Glu394Lys	missense_variant	Exon 2 of 7	2	NM_018364.5	ENSP00000261441.5
RSBN1	ENST00000612242.4	c.1180G>A	p.Glu394Lys	missense_variant	Exon 2 of 7	2		ENSP00000479490.1
RSBN1	ENST00000615321.1	c.1036G>A	p.Glu346Lys	missense_variant	Exon 2 of 7	2		ENSP00000480408.1
RSBN1	ENST00000476412.5	n.1036G>A		non_coding_transcript_exon_variant	Exon 2 of 8	2		ENSP00000433256.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459706 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726048

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1180G>A (p.E394K) 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 1180, causing the glutamic acid (E) at amino acid position 394 to be replaced by a lysine (K). 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	0.97
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.39	T;T;T;.
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	.;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.60	D;D;D;D
MetaSVM	Benign	-0.38	T
MutationAssessor	Uncertain	2.1	M;M;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.7	D;.;.;.
REVEL	Pathogenic	0.70
Sift	Benign	0.058	T;.;.;.
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		1.0	D;D;.;.
Vest4		0.82
MutPred		0.49		Gain of methylation at E394 (P = 0.0076);Gain of methylation at E394 (P = 0.0076);.;.;
MVP		0.18
MPC		2.6
ClinPred		0.98	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.60
gMVP		0.94

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: chr1-114340182;