22-21387144-C-T

Position:

• chr22-21387144-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001128635.2(RIMBP3B):​c.3286C>T​(p.Arg1096Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000069 (15 hom.)
  • Failed GnomAD Quality Control
• Consequence: RIMBP3B NM_001128635.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74

Genes affected

RIMBP3B (HGNC:33891): (RIMS binding protein 3B) Predicted to enable benzodiazepine receptor binding activity. Predicted to be involved in fertilization and spermatid development. Predicted to be located in cytoplasm. Predicted to be active in nucleus. Predicted to colocalize with manchette. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06811181).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIMBP3B	NM_001128635.2	c.3286C>T	p.Arg1096Cys	missense_variant	1/1	ENST00000620804.2	NP_001122107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIMBP3B	ENST00000620804.2	c.3286C>T	p.Arg1096Cys	missense_variant	1/1		NM_001128635.2	ENSP00000479326	P1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.0000565 AC: 6 AN: 106260 Hom.: 2 AF XY: 0.0000344 AC XY: 2 AN XY: 58178

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000933

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000134

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000693 AC: 40 AN: 577554 Hom.: 15 Cov.: 4 AF XY: 0.0000576 AC XY: 17 AN XY: 294940

Gnomad4 AFR exome AF: 0.000730

Gnomad4 AMR exome AF: 0.0000710

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000602

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000715

Gnomad4 OTH exome AF: 0.0000753

GnomAD4 genome Cov.: 0

Alfa AF: 0.0000843 Hom.: 0

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

Apr 25, 2023

The c.3286C>T (p.R1096C) alteration is located in exon 1 (coding exon 1) of the RIMBP3B gene. This alteration results from a C to T substitution at nucleotide position 3286, causing the arginine (R) at amino acid position 1096 to be replaced by a cysteine (C). 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	0.10
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Benign	0.80
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.14	N
MutationTaster	Benign	0.70	D;D
PrimateAI	Uncertain	0.50	T
Sift4G	Uncertain	0.055	T
Vest4		0.094
MVP		0.18
ClinPred		0.28	T
GERP RS		1.9
Varity_R		0.063
gMVP		0.36

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

LitVar

Other links and lift over

dbSNP: rs1328306345; hg19: chr22-21741433;