22-21387165-C-G

Variant names:

• chr22-21387165-C-G
• NM_001128635.2:c.3307C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001128635.2(RIMBP3B):​c.3307C>G​(p.Leu1103Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/19 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: 0.0000017 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RIMBP3B NM_001128635.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.53
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.25401556).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128635.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMBP3B	NM_001128635.2	MANE Select	c.3307C>G	p.Leu1103Val	missense	Exon 1 of 1	NP_001122107.1	A6NNM3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMBP3B	ENST00000620804.2	TSL:6 MANE Select	c.3307C>G	p.Leu1103Val	missense	Exon 1 of 1	ENSP00000479326.1	A6NNM3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000171 AC: 1 AN: 584410 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 298140

African (AFR) AF: 0.00 AC: 0 AN: 7864

American (AMR) AF: 0.00 AC: 0 AN: 28342

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12204

East Asian (EAS) AF: 0.00 AC: 0 AN: 34406

South Asian (SAS) AF: 0.00 AC: 0 AN: 66414

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2274

European-Non Finnish (NFE) AF: 0.00000261 AC: 1 AN: 382924

Other (OTH) AF: 0.00 AC: 0 AN: 26920

GnomAD4 genome Cov.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.057	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.5
PrimateAI	Uncertain	0.74	T
Sift4G	Uncertain	0.034	D
Vest4		0.39
MVP		0.21
ClinPred		0.78	D
GERP RS		1.9
Varity_R		0.058
gMVP		0.33
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

hg19: chr22-21741454;