22-23155487-T-C

Variant names:

• chr22-23155487-T-C
• rs5751592
• NM_004914.5:c.330-481T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004914.5(RAB36):​c.330-481T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 152,150 control chromosomes in the GnomAD database, including 48,490 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 0.80 (48490 hom., cov: 33)
• Consequence: RAB36 NM_004914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• Publications: 11 publications found

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]

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004914.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB36	NM_004914.5	MANE Select	c.330-481T>C		intron	N/A	NP_004905.3
	RAB36	NM_001349877.1		c.600-481T>C		intron	N/A	NP_001336806.1
	RAB36	NM_001349878.1		c.528-481T>C		intron	N/A	NP_001336807.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB36	ENST00000263116.8	TSL:1 MANE Select	c.330-481T>C		intron	N/A	ENSP00000263116.3
	RAB36	ENST00000341989.9	TSL:1	c.264-481T>C		intron	N/A	ENSP00000343494.5
	RAB36	ENST00000420895.1	TSL:3	c.210-481T>C		intron	N/A	ENSP00000397594.1

Frequencies

GnomAD3 genomes AF: 0.796 AC: 121010 AN: 152032 Hom.: 48437 Cov.: 33

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.774

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.796 AC: 121122 AN: 152150 Hom.: 48490 Cov.: 33 AF XY: 0.798 AC XY: 59384 AN XY: 74370

African (AFR) AF: 0.852 AC: 35368 AN: 41522

American (AMR) AF: 0.806 AC: 12328 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2532 AN: 3470

East Asian (EAS) AF: 0.991 AC: 5114 AN: 5160

South Asian (SAS) AF: 0.796 AC: 3836 AN: 4818

European-Finnish (FIN) AF: 0.726 AC: 7684 AN: 10586

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51693 AN: 67988

Other (OTH) AF: 0.776 AC: 1638 AN: 2110

Alfa AF: 0.773 Hom.: 190294

Bravo AF: 0.804

Asia WGS AF: 0.887 AC: 3085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.81
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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: rs5751592; hg19: chr22-23497674;