1-113797394-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018364.5(RSBN1):c.1346A>G(p.Glu449Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: RSBN1 NM_018364.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.773

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSBN1	NM_018364.5	c.1346A>G	p.Glu449Gly	missense_variant	2/7	ENST00000261441.9
RSBN1	XM_017001518.3	c.1346A>G	p.Glu449Gly	missense_variant	2/3
RSBN1	NR_130896.2	n.1410A>G		non_coding_transcript_exon_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSBN1	ENST00000261441.9	c.1346A>G	p.Glu449Gly	missense_variant	2/7	2	NM_018364.5	P1
RSBN1	ENST00000612242.4	c.1346A>G	p.Glu449Gly	missense_variant	2/7	2		P1
RSBN1	ENST00000615321.1	c.1202A>G	p.Glu401Gly	missense_variant	2/7	2
RSBN1	ENST00000476412.5	c.1202A>G	p.Glu401Gly	missense_variant, NMD_transcript_variant	2/8	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Aug 13, 2021

The c.1346A>G (p.E449G) 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 1346, causing the glutamic acid (E) at amino acid position 449 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	0.97
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.40
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D;D;T;.
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.0070	T
MetaRNN	Pathogenic	0.77	D;D;D;D
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Uncertain	2.8	M;M;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-6.3	D;.;.;.
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0020	D;.;.;.
Sift4G	Uncertain	0.022	D;D;D;D
Polyphen		1.0	D;D;.;.
Vest4		0.92
MutPred		0.44		Loss of stability (P = 0.0456);Loss of stability (P = 0.0456);.;.;
MVP		0.12
MPC		2.7
ClinPred		0.99	D
GERP RS		6.0
Varity_R		0.68
gMVP		0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-114340016;