22-21388617-A-G

Variant names:

• chr22-21388617-A-G
• rs1922279348
• NM_001128635.2:c.4759A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001128635.2(RIMBP3B):​c.4759A>G​(p.Met1587Val) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M1587I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 15)
  • Exomes 𝑓: 0.000025 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RIMBP3B NM_001128635.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.628
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04253763).

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.4759A>G	p.Met1587Val	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.4759A>G	p.Met1587Val	missense	Exon 1 of 1	ENSP00000479326.1	A6NNM3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 101068 Hom.: 0 Cov.: 15

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: 0.00

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: 0.0000251 AC: 32 AN: 1277132 Hom.: 0 Cov.: 18 AF XY: 0.0000360 AC XY: 23 AN XY: 638398

⚠️ 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: 30090

American (AMR) AF: 0.00 AC: 0 AN: 34630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23666

East Asian (EAS) AF: 0.00 AC: 0 AN: 37156

South Asian (SAS) AF: 0.000382 AC: 29 AN: 75964

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3756

European-Non Finnish (NFE) AF: 0.00000207 AC: 2 AN: 967100

Other (OTH) AF: 0.0000186 AC: 1 AN: 53736

⚠️ 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: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 101068 Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0 AN XY: 47518

African (AFR) AF: 0.00 AC: 0 AN: 27482

American (AMR) AF: 0.00 AC: 0 AN: 8510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2758

East Asian (EAS) AF: 0.00 AC: 0 AN: 2548

South Asian (SAS) AF: 0.00 AC: 0 AN: 1674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5638

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 74

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 50528

Other (OTH) AF: 0.00 AC: 0 AN: 1166

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	0.075
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	2.1
DANN	Benign	0.33
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.00040	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N
PhyloP100		0.63
PrimateAI	Uncertain	0.51	T
Sift4G	Benign	0.19	T
Vest4		0.094
MVP		0.014
ClinPred		0.065	T
GERP RS		2.0
Varity_R		0.096
gMVP		0.37
Mutation Taster		=96/4	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: rs1922279348; hg19: chr22-21742906;