rs200820954

Variant names:

• chr9-125220580-C-G
• rs200820954
• NM_005833.4:c.406C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-125220580-C-G
• chr9-125220580-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_005833.4(RABEPK):​c.406C>G​(p.Pro136Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000496 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P136S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000044 (0 hom.)
• Consequence: RABEPK NM_005833.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.58
• Publications: 2 publications found

Genes affected

RABEPK (HGNC:16896): (Rab9 effector protein with kelch motifs) Predicted to be involved in receptor-mediated endocytosis and vesicle docking involved in exocytosis. Predicted to be located in cytoplasmic vesicle; cytosol; and trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.795

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005833.4. 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
	RABEPK	NM_005833.4	MANE Select	c.406C>G	p.Pro136Ala	missense	Exon 5 of 8	NP_005824.2
	RABEPK	NM_001174152.2		c.406C>G	p.Pro136Ala	missense	Exon 6 of 9	NP_001167623.1	Q7Z6M1-1
	RABEPK	NM_001174153.2		c.253C>G	p.Pro85Ala	missense	Exon 5 of 8	NP_001167624.1	Q7Z6M1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABEPK	ENST00000373538.8	TSL:1 MANE Select	c.406C>G	p.Pro136Ala	missense	Exon 5 of 8	ENSP00000362639.3	Q7Z6M1-1
	RABEPK	ENST00000394125.8	TSL:1	c.406C>G	p.Pro136Ala	missense	Exon 6 of 9	ENSP00000377683.4	Q7Z6M1-1
	RABEPK	ENST00000259460.12	TSL:1	c.253C>G	p.Pro85Ala	missense	Exon 5 of 8	ENSP00000259460.8	Q7Z6M1-2

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152194 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000517 AC: 13 AN: 251302 AF XY: 0.0000663

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000445 AC: 65 AN: 1461850 Hom.: 0 Cov.: 32 AF XY: 0.0000413 AC XY: 30 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000567 AC: 63 AN: 1111982

Other (OTH) AF: 0.0000331 AC: 2 AN: 60394

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152194 Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11 AN XY: 74348

African (AFR) AF: 0.0000482 AC: 2 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000847 Hom.: 0

Bravo AF: 0.000110

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.000273

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.085	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Uncertain	0.49	D
MutationAssessor	Pathogenic	3.8	H
PhyloP100		6.6
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-7.1	D
REVEL	Uncertain	0.41
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.72
MVP		0.89
MPC		0.24
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.91
gMVP		0.62
Mutation Taster		=69/31	polymorphism

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: rs200820954; hg19: chr9-127982859;