1-113797839-T-C

Position:

• chr1-113797839-T-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.901A>G​(p.Thr301Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 2.20

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=0.059305638).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSBN1	NM_018364.5	c.901A>G	p.Thr301Ala	missense_variant	2/7	ENST00000261441.9
RSBN1	XM_017001518.3	c.901A>G	p.Thr301Ala	missense_variant	2/3
RSBN1	NR_130896.2	n.965A>G		non_coding_transcript_exon_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSBN1	ENST00000261441.9	c.901A>G	p.Thr301Ala	missense_variant	2/7	2	NM_018364.5	P1
RSBN1	ENST00000612242.4	c.901A>G	p.Thr301Ala	missense_variant	2/7	2		P1
RSBN1	ENST00000615321.1	c.757A>G	p.Thr253Ala	missense_variant	2/7	2
RSBN1	ENST00000476412.5	c.757A>G	p.Thr253Ala	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 01, 2022

The c.901A>G (p.T301A) 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 901, causing the threonine (T) at amino acid position 301 to be replaced by an alanine (A). 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	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Benign	0.93
DEOGEN2	Benign	0.022	T;T;T;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.66	.;T;T;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.059	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.69	N;N;.;.
MutationTaster	Benign	0.61	N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.56	N;.;.;.
REVEL	Benign	0.069
Sift	Benign	0.19	T;.;.;.
Sift4G	Benign	0.81	T;T;T;T
Polyphen		0.015	B;B;.;.
Vest4		0.15
MutPred		0.29		Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);.;.;
MVP		0.043
MPC		0.33
ClinPred		0.12	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.030
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr1-114340461;