22-23162772-C-T

Position:

• chr22-23162772-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
RAB36	NM_004914.5	c.*1208C>T		3_prime_UTR_variant	11/11	ENST00000263116.8	NP_004905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB36	ENST00000263116.8	c.*1208C>T		3_prime_UTR_variant	11/11	1	NM_004914.5	ENSP00000263116	P1

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84225 AN: 151942 Hom.: 24082 Cov.: 33

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

GnomAD3 exomes AF: 0.534 AC: 69833 AN: 130782 Hom.: 18920 AF XY: 0.536 AC XY: 38288 AN XY: 71370

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 SAS exome AF: 0.592

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.: 0 AF XY: 0.529 AC XY: 91551 AN XY: 172936

Gnomad4 AFR exome AF: 0.679

Gnomad4 AMR exome AF: 0.510

Gnomad4 ASJ exome AF: 0.491

Gnomad4 EAS exome AF: 0.640

Gnomad4 SAS exome AF: 0.599

Gnomad4 FIN exome AF: 0.434

Gnomad4 NFE exome AF: 0.489

Gnomad4 OTH exome AF: 0.519

GnomAD4 genome AF: 0.554 AC: 84311 AN: 152062 Hom.: 24113 Cov.: 33 AF XY: 0.555 AC XY: 41230 AN XY: 74354

Gnomad4 AFR AF: 0.691

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.647

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.436

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.536

Alfa AF: 0.509 Hom.: 21485

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
DANN	Benign	0.57

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

LitVar

Other links and lift over

dbSNP: rs5759621; hg19: chr22-23504959; COSMIC: COSV54075117; COSMIC: COSV54075117;