chr22-21545903-A-G

Variant names:

• chr22-21545903-A-G
• rs7926
• NM_001128633.2:c.*154T>C

Variant summary

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

The NM_001128633.2(RIMBP3C):​c.*154T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000081 (0 hom., cov: 15)
  • Failed GnomAD Quality Control
• Consequence: RIMBP3C NM_001128633.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 2 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 (BayesDel_noAF=-0.99).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIMBP3C	NM_001128633.2	c.*154T>C		3_prime_UTR_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.*154T>C		3_prime_UTR_variant	Exon 1 of 1	6	NM_001128633.2	ENSP00000390630.1

Frequencies

GnomAD3 genomes AF: 0.0000725 AC: 9 AN: 124176 Hom.: 0 Cov.: 15

Gnomad AFR AF: 0.000192

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000756

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000420

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000597

GnomAD4 exome Cov.: 19

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000805 AC: 10 AN: 124218 Hom.: 0 Cov.: 15 AF XY: 0.0000661 AC XY: 4 AN XY: 60538

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000230 AC: 6 AN: 26036

American (AMR) AF: 0.0000755 AC: 1 AN: 13244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3134

East Asian (EAS) AF: 0.000421 AC: 2 AN: 4748

South Asian (SAS) AF: 0.00 AC: 0 AN: 3848

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 256

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 61112

Other (OTH) AF: 0.000589 AC: 1 AN: 1698

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000000686118), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00228 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.17
DANN	Benign	0.48
PhyloP100		-1.5

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: rs7926; hg19: chr22-21900192;