Genetic Variant RAB36:c.*1208C>T (chr22-23162772-C-T) – 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.*1208C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 455,774 control chromosomes in the GnomAD database, including 66,128 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 0.55 ( 24113 hom., cov: 33)

Exomes 𝑓: 0.52 ( 42015 hom. )

Consequence

RAB36
NM_004914.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.378

Publications

11 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=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB36	NM_004914.5 link	c.*1208C>T		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.*1208C>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_004914.5	ENSP00000263116.3		O95755

Frequencies

GnomAD3 genomes

AF:

0.554

AC:

84225

AN:

151942

Hom.:

24082

Cov.:

show subpopulations

Gnomad AFR

AF:

0.691

Gnomad AMI

AF:

0.594

Gnomad AMR

AF:

0.493

Gnomad ASJ

AF:

0.486

Gnomad EAS

AF:

0.647

Gnomad SAS

AF:

0.597

Gnomad FIN

AF:

0.436

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.497

Gnomad OTH

AF:

0.531

GnomAD2 exomes

AF:

0.534

AC:

69833

AN:

130782

AF XY:

0.536

show subpopulations

Gnomad AFR exome

AF:

0.695

Gnomad AMR exome

AF:

0.511

Gnomad ASJ exome

AF:

0.494

Gnomad EAS exome

AF:

0.646

Gnomad FIN exome

AF:

0.440

Gnomad NFE exome

AF:

0.494

Gnomad OTH exome

AF:

0.521

GnomAD4 exome

AF:

0.522

AC:

158603

AN:

303712

Hom.:

42015

Cov.:

AF XY:

0.529

AC XY:

91551

AN XY:

172936

show subpopulations

African (AFR)

AF:

0.679

AC:

5854

AN:

8620

American (AMR)

AF:

0.510

AC:

13911

AN:

27262

Ashkenazi Jewish (ASJ)

AF:

0.491

AC:

5300

AN:

10786

East Asian (EAS)

AF:

0.640

AC:

5885

AN:

9192

South Asian (SAS)

AF:

0.599

AC:

35784

AN:

59696

European-Finnish (FIN)

AF:

0.434

AC:

5368

AN:

12364

Middle Eastern (MID)

AF:

0.527

AC:

1467

AN:

2782

European-Non Finnish (NFE)

AF:

0.489

AC:

77651

AN:

158786

Other (OTH)

AF:

0.519

AC:

7383

AN:

14224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.413

Heterozygous variant carriers

4846

9692

14538

19384

24230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

522

1044

1566

2088

2610

<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:

0.554

AC:

84311

AN:

152062

Hom.:

24113

Cov.:

AF XY:

0.555

AC XY:

41230

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.691

AC:

28655

AN:

41468

American (AMR)

AF:

0.493

AC:

7534

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.486

AC:

1688

AN:

3470

East Asian (EAS)

AF:

0.647

AC:

3348

AN:

5176

South Asian (SAS)

AF:

0.598

AC:

2883

AN:

4822

European-Finnish (FIN)

AF:

0.436

AC:

4600

AN:

10562

Middle Eastern (MID)

AF:

0.554

AC:

163

AN:

294

European-Non Finnish (NFE)

AF:

0.497

AC:

33769

AN:

67962

Other (OTH)

AF:

0.536

AC:

1132

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1848

3697

5545

7394

9242

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

728

1456

2184

2912

3640

<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:

0.515

Hom.:

28246

Bravo

AF:

0.561

Asia WGS

AF:

0.614

AC:

2136

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

2.1

(source)

DANN

Benign

0.57

PhyloP100

-0.38

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