chr22-21546073-G-A

Variant names:

• chr22-21546073-G-A
• rs1926052698
• NM_001128633.2:c.4904C>T

Variant summary

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

The NM_001128633.2(RIMBP3C):​c.4904C>T​(p.Ser1635Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 6)
  • Exomes 𝑓: 0.0000043 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RIMBP3C NM_001128633.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.51
• Publications: 0 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19602937).

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.4904C>T	p.Ser1635Phe	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.4904C>T	p.Ser1635Phe	missense	Exon 1 of 1	ENSP00000390630.1	A6NJZ7

Frequencies

GnomAD3 genomes Cov.: 6

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000428 AC: 2 AN: 467566 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 238544

African (AFR) AF: 0.00 AC: 0 AN: 5178

American (AMR) AF: 0.000156 AC: 2 AN: 12860

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8770

East Asian (EAS) AF: 0.00 AC: 0 AN: 24622

South Asian (SAS) AF: 0.00 AC: 0 AN: 38698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1528

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 322272

Other (OTH) AF: 0.00 AC: 0 AN: 21294

GnomAD4 genome Cov.: 6

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	0.16
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.55	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.5
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.090
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.016	D
Vest4		0.18
MVP		0.20
ClinPred		0.80	D
GERP RS		2.3
Varity_R		0.053
gMVP		0.32
Mutation Taster		=92/8	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: rs1926052698; hg19: chr22-21900362;