Genetic Variant NM_004914.5:c.*2183T>C (chr22-23163747-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004914.5(RAB36):c.*2183T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,542 control chromosomes in the GnomAD database, including 19,584 homozygotes. 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 0.51 ( 19584 hom., cov: 32)

Exomes 𝑓: 0.50 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

RAB36
NM_004914.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.80

Publications

8 publications found

Variant links:

Genes affected

RAB36 (HGNC:9775): (RAB36, member RAS oncogene family) Predicted to enable GTP binding activity and GTPase activity. Predicted to be involved in protein transport. Predicted to be located in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

RAB36 links:

RSPH14 (HGNC:13437): (radial spoke head 14 homolog) This gene encodes a protein with no known function but with slight similarity to a yeast vacuolar protein. The gene is located in a region deleted in pediatric rhabdoid tumors of the brain, kidney and soft tissues, but mutations in this gene have not been associated with the disease. [provided by RefSeq, Jul 2008]

RSPH14 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB36	NM_004914.5 link	c.*2183T>C		3_prime_UTR_variant	Exon 11 of 11	ENST00000263116.8	NP_004905.3	O95755

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB36	ENST00000263116.8 link	c.*2183T>C		3_prime_UTR_variant	Exon 11 of 11	1	NM_004914.5	ENSP00000263116.3		O95755

Frequencies

GnomAD3 genomes

AF:

0.507

AC:

76754

AN:

151422

Hom.:

19555

Cov.:

show subpopulations

Gnomad AFR

AF:

0.540

Gnomad AMI

AF:

0.589

Gnomad AMR

AF:

0.479

Gnomad ASJ

AF:

0.484

Gnomad EAS

AF:

0.617

Gnomad SAS

AF:

0.592

Gnomad FIN

AF:

0.418

Gnomad MID

AF:

0.564

Gnomad NFE

AF:

0.493

Gnomad OTH

AF:

0.502

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.550

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.507

AC:

76834

AN:

151542

Hom.:

19584

Cov.:

AF XY:

0.508

AC XY:

37607

AN XY:

74032

show subpopulations

African (AFR)

AF:

0.540

AC:

22271

AN:

41254

American (AMR)

AF:

0.479

AC:

7301

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.484

AC:

1676

AN:

3464

East Asian (EAS)

AF:

0.616

AC:

3168

AN:

5142

South Asian (SAS)

AF:

0.594

AC:

2861

AN:

4820

European-Finnish (FIN)

AF:

0.418

AC:

4402

AN:

10538

Middle Eastern (MID)

AF:

0.555

AC:

162

AN:

292

European-Non Finnish (NFE)

AF:

0.493

AC:

33394

AN:

67790

Other (OTH)

AF:

0.508

AC:

1070

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1968

3936

5904

7872

9840

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

694

1388

2082

2776

3470

<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:

0.499

Hom.:

18685

Bravo

AF:

0.509

Asia WGS

AF:

0.596

AC:

2075

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.23

(source)

DANN

Benign

0.42

PhyloP100

-1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over