22-23161683-A-G

Variant names:

• chr22-23161683-A-G
• rs737820
• NM_004914.5:c.*119A>G

Variant summary

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

The NM_004914.5(RAB36):​c.*119A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 868,854 control chromosomes in the GnomAD database, including 105,981 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 (20102 hom., cov: 33)
  • Exomes 𝑓: 0.49 (85879 hom.)
• Consequence: RAB36 NM_004914.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.764
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB36	NM_004914.5	MANE Select	c.*119A>G		3_prime_UTR	Exon 11 of 11	NP_004905.3
	RAB36	NM_001349877.1		c.*119A>G		3_prime_UTR	Exon 12 of 12	NP_001336806.1
	RAB36	NM_001349878.1		c.*60A>G		3_prime_UTR	Exon 11 of 11	NP_001336807.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB36	ENST00000263116.8	TSL:1 MANE Select	c.*119A>G		3_prime_UTR	Exon 11 of 11	ENSP00000263116.3	O95755-1
	RAB36	ENST00000857885.1		c.*119A>G		3_prime_UTR	Exon 12 of 12	ENSP00000527944.1
	RAB36	ENST00000857886.1		c.*119A>G		3_prime_UTR	Exon 11 of 11	ENSP00000527945.1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77759 AN: 151924 Hom.: 20075 Cov.: 33

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.506

GnomAD4 exome AF: 0.485 AC: 347785 AN: 716812 Hom.: 85879 Cov.: 9 AF XY: 0.491 AC XY: 179442 AN XY: 365650

African (AFR) AF: 0.512 AC: 9092 AN: 17774

American (AMR) AF: 0.470 AC: 12582 AN: 26792

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 7894 AN: 16458

East Asian (EAS) AF: 0.626 AC: 19517 AN: 31178

South Asian (SAS) AF: 0.592 AC: 32371 AN: 54676

European-Finnish (FIN) AF: 0.426 AC: 12606 AN: 29574

Middle Eastern (MID) AF: 0.525 AC: 1366 AN: 2602

European-Non Finnish (NFE) AF: 0.468 AC: 235367 AN: 503292

Other (OTH) AF: 0.493 AC: 16990 AN: 34466

GnomAD4 genome AF: 0.512 AC: 77838 AN: 152042 Hom.: 20102 Cov.: 33 AF XY: 0.514 AC XY: 38174 AN XY: 74312

African (AFR) AF: 0.542 AC: 22491 AN: 41486

American (AMR) AF: 0.479 AC: 7317 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1688 AN: 3472

East Asian (EAS) AF: 0.649 AC: 3330 AN: 5134

South Asian (SAS) AF: 0.597 AC: 2877 AN: 4820

European-Finnish (FIN) AF: 0.436 AC: 4602 AN: 10566

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33751 AN: 67960

Other (OTH) AF: 0.511 AC: 1077 AN: 2108

Alfa AF: 0.501 Hom.: 7439

Bravo AF: 0.512

Asia WGS AF: 0.606 AC: 2109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.4
DANN	Benign	0.55
PhyloP100		-0.76
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: rs737820; hg19: chr22-23503870; COSMIC: COSV54076674; COSMIC: COSV54076674;