Genetic Variant NM_001128633.2:c.3196_3201dupCAGGTG (chr22-21547775-A-ACACCTG) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 2P and 9B. PM4BP6BA1

The NM_001128633.2(RIMBP3C):c.3196_3201dupCAGGTG(p.Val1067_Tyr1068insGlnVal) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.40 ( 62 hom., cov: 0)

Exomes 𝑓: 0.32 ( 1955 hom. )

Failed GnomAD Quality Control

Consequence

RIMBP3C
NM_001128633.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign no assertion criteria provided B:2

Conservation

PhyloP100: -0.0600

Publications

0 publications found

Variant links:

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]

RIMBP3C links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001128633.2.

BP6

Variant 22-21547775-A-ACACCTG is Benign according to our data. Variant chr22-21547775-A-ACACCTG is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1205884.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

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.3196_3201dupCAGGTG	p.Val1067_Tyr1068insGlnVal	conservative_inframe_insertion	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.3196_3201dupCAGGTG	p.Val1067_Tyr1068insGlnVal	conservative_inframe_insertion	Exon 1 of 1	ENSP00000390630.1	A6NJZ7

Frequencies

GnomAD3 genomes

AF:

0.409

AC:

134

AN:

328

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.333

Gnomad AMI

AF:

0.667

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

1.00

Gnomad NFE

AF:

0.880

Gnomad OTH

AF:

0.400

GnomAD2 exomes

AF:

0.285

AC:

361

AN:

1266

AF XY:

0.274

show subpopulations

Gnomad AFR exome

AF:

0.567

Gnomad AMR exome

AF:

0.371

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.882

Gnomad NFE exome

AF:

0.906

Gnomad OTH exome

AF:

0.263

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.323

AC:

4065

AN:

12584

Hom.:

1955

Cov.:

AF XY:

0.279

AC XY:

2055

AN XY:

7356

show subpopulations

African (AFR)

AF:

0.470

AC:

187

AN:

398

American (AMR)

AF:

0.417

AC:

185

AN:

444

Ashkenazi Jewish (ASJ)

AF:

0.971

AC:

101

AN:

104

East Asian (EAS)

AF:

0.00

AC:

AN:

2580

South Asian (SAS)

AF:

0.0794

AC:

353

AN:

4448

European-Finnish (FIN)

AF:

0.655

AC:

443

AN:

676

Middle Eastern (MID)

AF:

0.950

AC:

AN:

European-Non Finnish (NFE)

AF:

0.804

AC:

2554

AN:

3176

Other (OTH)

AF:

0.284

AC:

204

AN:

718

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.790

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.404

AC:

134

AN:

332

Hom.:

Cov.:

AF XY:

0.393

AC XY:

AN XY:

178

show subpopulations

African (AFR)

AF:

0.333

AC:

AN:

American (AMR)

AF:

0.160

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.185

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.880

AC:

AN:

100

Other (OTH)

AF:

0.333

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.770

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.364

Hom.:

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.060

Mutation Taster

=85/15

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over