rs1922264389

Variant names:

• chr22-21388180-G-A
• rs1922264389
• NM_001128635.2:c.4322G>A

Variant summary

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

The NM_001128635.2(RIMBP3B):​c.4322G>A​(p.Gly1441Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000068 (0 hom., cov: 6)
  • Exomes 𝑓: 0.00027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RIMBP3B NM_001128635.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0350
• 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=0.09064412).

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.4322G>A	p.Gly1441Asp	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.4322G>A	p.Gly1441Asp	missense	Exon 1 of 1	ENSP00000479326.1	A6NNM3

Frequencies

GnomAD3 genomes AF: 0.0000678 AC: 3 AN: 44272 Hom.: 0 Cov.: 6

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00291

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000272 AC: 128 AN: 470822 Hom.: 0 Cov.: 4 AF XY: 0.000386 AC XY: 96 AN XY: 248660

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 13434

American (AMR) AF: 0.00 AC: 0 AN: 24158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14682

East Asian (EAS) AF: 0.00 AC: 0 AN: 31392

South Asian (SAS) AF: 0.00245 AC: 118 AN: 48136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32096

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2040

European-Non Finnish (NFE) AF: 0.0000252 AC: 7 AN: 277990

Other (OTH) AF: 0.000112 AC: 3 AN: 26894

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000677 AC: 3 AN: 44308 Hom.: 0 Cov.: 6 AF XY: 0.000104 AC XY: 2 AN XY: 19310

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 11910

American (AMR) AF: 0.00 AC: 0 AN: 4264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1174

East Asian (EAS) AF: 0.00 AC: 0 AN: 1480

South Asian (SAS) AF: 0.00293 AC: 3 AN: 1024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 204

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 19774

Other (OTH) AF: 0.00 AC: 0 AN: 584

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0338994), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 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	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	1.4
DANN	Benign	0.83
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.035
PrimateAI	Benign	0.38	T
Sift4G	Uncertain	0.054	T
Vest4		0.11
MVP		0.030
ClinPred		0.96	D
GERP RS		-1.6
Varity_R		0.034
gMVP		0.36
Mutation Taster		=95/5	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

dbSNP: rs1922264389; hg19: chr22-21742469;