1-113767175-A-G

Position:

• chr1-113767175-A-G

Variant summary

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

The NM_018364.5(RSBN1):​c.1859T>C​(p.Ile620Thr) 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: 8.95

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	Protein	UniProt
RSBN1	NM_018364.5	c.1859T>C	p.Ile620Thr	missense_variant	6/7	ENST00000261441.9	NP_060834.2
RSBN1	NR_130896.2	n.2041T>C		non_coding_transcript_exon_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSBN1	ENST00000261441.9	c.1859T>C	p.Ile620Thr	missense_variant	6/7	2	NM_018364.5	ENSP00000261441.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Sep 27, 2024

The c.1859T>C (p.I620T) alteration is located in exon 6 (coding exon 6) of the RSBN1 gene. This alteration results from a T to C substitution at nucleotide position 1859, causing the isoleucine (I) at amino acid position 620 to be replaced by a threonine (T). 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	0.85
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T;T;T;.
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	.;D;D;D
M_CAP	Benign	0.0045	T
MetaRNN	Uncertain	0.50	D;D;D;D
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.7	L;L;.;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.7	D;.;.;.
REVEL	Uncertain	0.41
Sift	Uncertain	0.0020	D;.;.;.
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		0.56	P;P;.;.
Vest4		0.66
MutPred		0.59		Loss of stability (P = 0.0425);Loss of stability (P = 0.0425);.;.;
MVP		0.082
MPC		2.0
ClinPred		0.98	D
GERP RS		5.9
Varity_R		0.51
gMVP		0.77

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: chr1-114309797;