1-113797674-A-G

Variant summary

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

The NM_018364.5(RSBN1):c.1066T>C(p.Phe356Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 9.32

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/exons	MANE	UniProt
RSBN1	NM_018364.5	c.1066T>C	p.Phe356Leu	missense_variant	2/7	ENST00000261441.9
RSBN1	XM_017001518.3	c.1066T>C	p.Phe356Leu	missense_variant	2/3
RSBN1	NR_130896.2	n.1130T>C		non_coding_transcript_exon_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSBN1	ENST00000261441.9	c.1066T>C	p.Phe356Leu	missense_variant	2/7	2	NM_018364.5	P1
RSBN1	ENST00000612242.4	c.1066T>C	p.Phe356Leu	missense_variant	2/7	2		P1
RSBN1	ENST00000615321.1	c.922T>C	p.Phe308Leu	missense_variant	2/7	2
RSBN1	ENST00000476412.5	c.922T>C	p.Phe308Leu	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

Dec 06, 2023

The c.1066T>C (p.F356L) alteration is located in exon 2 (coding exon 2) of the RSBN1 gene. This alteration results from a T to C substitution at nucleotide position 1066, causing the phenylalanine (F) at amino acid position 356 to be replaced by a leucine (L). 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	0.99
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Benign	0.30	T;T;T;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	1.0	D
M_CAP	Benign	0.0029	T
MetaRNN	Uncertain	0.62	D;D;D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.8	L;L;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-4.7	D;.;.;.
REVEL	Uncertain	0.35
Sift	Benign	0.084	T;.;.;.
Sift4G	Benign	0.066	T;T;T;T
Polyphen		0.93	P;P;.;.
Vest4		0.86
MutPred		0.47		Loss of methylation at K355 (P = 0.0294);Loss of methylation at K355 (P = 0.0294);.;.;
MVP		0.082
MPC		0.45
ClinPred		0.97	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.55
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: chr1-114340296;