chr22-21387646-A-C

Variant names:

• chr22-21387646-A-C
• rs201550629
• NM_001128635.2:c.3788A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001128635.2(RIMBP3B):​c.3788A>C​(p.Glu1263Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.25 (0 hom., cov: 0)
  • Exomes 𝑓: 0.17 (1248 hom.)
  • Failed GnomAD Quality Control
• Consequence: RIMBP3B NM_001128635.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.92
• Publications: 2 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10921261).
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

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.3788A>C	p.Glu1263Ala	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.3788A>C	p.Glu1263Ala	missense	Exon 1 of 1	ENSP00000479326.1	A6NNM3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0

Gnomad EAS AF: 0.00

GnomAD4 exome AF: 0.165 AC: 14386 AN: 87098 Hom.: 1248 Cov.: 0 AF XY: 0.164 AC XY: 8209 AN XY: 50050

African (AFR) AF: 0.121 AC: 105 AN: 870

American (AMR) AF: 0.346 AC: 2269 AN: 6560

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 220 AN: 1822

East Asian (EAS) AF: 0.314 AC: 3464 AN: 11036

South Asian (SAS) AF: 0.163 AC: 4168 AN: 25498

European-Finnish (FIN) AF: 0.0983 AC: 302 AN: 3072

Middle Eastern (MID) AF: 0.187 AC: 59 AN: 316

European-Non Finnish (NFE) AF: 0.0930 AC: 3142 AN: 33782

Other (OTH) AF: 0.159 AC: 657 AN: 4142

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

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: 0.0390 Hom.: 13

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	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.9
PrimateAI	Benign	0.42	T
Sift4G	Benign	0.34	T
Vest4		0.16
MVP		0.072
ClinPred		0.57	D
GERP RS		3.2
Varity_R		0.066
gMVP		0.34
Mutation Taster		=100/0	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: rs201550629; hg19: chr22-21741935; COSMIC: COSV63115743; COSMIC: COSV63115743;