1-113766075-G-C

Position:

• chr1-113766075-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018364.5(RSBN1):​c.2314C>G​(p.Gln772Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign 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: 5.19

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058802605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSBN1	NM_018364.5	c.2314C>G	p.Gln772Glu	missense_variant	7/7	ENST00000261441.9
RSBN1	NR_130896.2	n.2496C>G		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSBN1	ENST00000261441.9	c.2314C>G	p.Gln772Glu	missense_variant	7/7	2	NM_018364.5	P1
RSBN1	ENST00000612242.4	c.2314C>G	p.Gln772Glu	missense_variant	7/7	2		P1
RSBN1	ENST00000615321.1	c.2170C>G	p.Gln724Glu	missense_variant	7/7	2
RSBN1	ENST00000476412.5	c.*1052C>G		3_prime_UTR_variant, NMD_transcript_variant	8/8	2

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

May 23, 2023

The c.2314C>G (p.Q772E) alteration is located in exon 7 (coding exon 7) of the RSBN1 gene. This alteration results from a C to G substitution at nucleotide position 2314, causing the glutamine (Q) at amino acid position 772 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	Benign	0.064
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.020	T;T;T;.
Eigen	Benign	-0.16
Eigen_PC	Benign	0.034
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.059	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L;.;.
MutationTaster	Benign	0.97	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.39	N;.;.;.
REVEL	Benign	0.11
Sift	Benign	0.52	T;.;.;.
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	B;B;.;.
Vest4		0.12
MutPred		0.049		Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);.;.;
MVP		0.043
MPC		0.013
ClinPred		0.27	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.061
gMVP		0.16

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: chr1-114308697;