22-21546073-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIMBP3C	NM_001128633.2	c.4904C>T	p.Ser1635Phe	missense_variant	Exon 1 of 1	ENST00000433039.2	NP_001122105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIMBP3C	ENST00000433039.2	c.4904C>T	p.Ser1635Phe	missense_variant	Exon 1 of 1	6	NM_001128633.2	ENSP00000390630.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000156

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 6

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 18, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4904C>T (p.S1635F) alteration is located in exon 1 (coding exon 1) of the RIMBP3C gene. This alteration results from a C to T substitution at nucleotide position 4904, causing the serine (S) at amino acid position 1635 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	.;M
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.090
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.016	D;D
Vest4		0.18
MVP		0.20
ClinPred		0.80	D
GERP RS		2.3
Varity_R		0.053
gMVP		0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs1926052698; hg19: chr22-21900362;