chr9-122957204-C-T

Variant names:

• chr9-122957204-C-T
• NM_012197.4:c.145C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012197.4(RABGAP1):​c.145C>T​(p.Leu49Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RABGAP1 NM_012197.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.71
• Publications: 0 publications found

Genes affected

RABGAP1 (HGNC:17155): (RAB GTPase activating protein 1) Enables GTPase activator activity and small GTPase binding activity. Involved in regulation of GTPase activity. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

RABGAP1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012197.4. 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
	RABGAP1	NM_012197.4	MANE Select	c.145C>T	p.Leu49Phe	missense	Exon 2 of 26	NP_036329.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABGAP1	ENST00000373647.9	TSL:1 MANE Select	c.145C>T	p.Leu49Phe	missense	Exon 2 of 26	ENSP00000362751.4	Q9Y3P9-1
	RABGAP1	ENST00000870248.1		c.145C>T	p.Leu49Phe	missense	Exon 2 of 27	ENSP00000540307.1
	RABGAP1	ENST00000941860.1		c.145C>T	p.Leu49Phe	missense	Exon 2 of 27	ENSP00000611919.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1374376 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 678352

African (AFR) AF: 0.00 AC: 0 AN: 32574

American (AMR) AF: 0.00 AC: 0 AN: 43328

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23926

East Asian (EAS) AF: 0.00 AC: 0 AN: 38564

South Asian (SAS) AF: 0.00 AC: 0 AN: 72594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5404

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1053218

Other (OTH) AF: 0.00 AC: 0 AN: 55636

GnomAD4 genome Cov.: 32

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	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.7
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.074	T
Polyphen		0.99	D
Vest4		0.73
MutPred		0.43		Gain of methylation at K50 (P = 0.0379)
MVP		0.52
MPC		0.0074
ClinPred		0.92	D
GERP RS		4.9
Varity_R		0.30
gMVP		0.34
Mutation Taster		=60/40	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

hg19: chr9-125719483;