chr22-21547058-G-T

Variant names:

• chr22-21547058-G-T
• rs2242314
• NM_001128633.2:c.3919C>A

Variant summary

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

The NM_001128633.2(RIMBP3C):​c.3919C>A​(p.Pro1307Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 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: 0.58 (6166 hom.)
  • Failed GnomAD Quality Control
• Consequence: RIMBP3C NM_001128633.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.31
• Publications: 3 publications found

Genes affected

RIMBP3C (HGNC:33892): (RIMS binding protein 3C) 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=0.060838252).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128633.2. 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
	RIMBP3C	NM_001128633.2	MANE Select	c.3919C>A	p.Pro1307Thr	missense	Exon 1 of 1	NP_001122105.1	A6NJZ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMBP3C	ENST00000433039.2	TSL:6 MANE Select	c.3919C>A	p.Pro1307Thr	missense	Exon 1 of 1	ENSP00000390630.1	A6NJZ7

Frequencies

GnomAD3 genomes AC: 0 AN: 0 Hom.: 0 Cov.: 0

GnomAD2 exomes AF: 0.00 AC: 0 AN: 22 AF XY: 0.00

Gnomad EAS exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.578 AC: 26611 AN: 46062 Hom.: 6166 Cov.: 0 AF XY: 0.574 AC XY: 13614 AN XY: 23710

African (AFR) AF: 0.360 AC: 989 AN: 2746

American (AMR) AF: 0.671 AC: 2119 AN: 3156

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 554 AN: 888

East Asian (EAS) AF: 0.702 AC: 1211 AN: 1724

South Asian (SAS) AF: 0.492 AC: 2552 AN: 5182

European-Finnish (FIN) AF: 0.623 AC: 855 AN: 1372

Middle Eastern (MID) AF: 0.561 AC: 83 AN: 148

European-Non Finnish (NFE) AF: 0.592 AC: 16892 AN: 28540

Other (OTH) AF: 0.588 AC: 1356 AN: 2306

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

Alfa AF: 0.515 Hom.: 590

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	0.066
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.35
DANN	Benign	0.89
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-1.3
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.013
Sift	Benign	0.044	D
Sift4G	Uncertain	0.044	D
Vest4		0.14
MVP		0.014
ClinPred		0.055	T
GERP RS		-5.4
Varity_R		0.034
gMVP		0.23
Mutation Taster		=99/1	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: rs2242314; hg19: chr22-21901347;