9-122996602-T-G

Variant names:

• chr9-122996602-T-G
• NM_012197.4:c.1098T>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012197.4(RABGAP1):​c.1098T>G​(p.Asp366Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RABGAP1 NM_012197.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.268

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABGAP1	NM_012197.4	c.1098T>G	p.Asp366Glu	missense_variant	Exon 8 of 26	ENST00000373647.9	NP_036329.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RABGAP1	ENST00000373647.9	c.1098T>G	p.Asp366Glu	missense_variant	Exon 8 of 26	1	NM_012197.4	ENSP00000362751.4
RABGAP1	ENST00000426918.2	n.*662T>G		non_coding_transcript_exon_variant	Exon 7 of 8	5		ENSP00000416327.2
RABGAP1	ENST00000456584.5	n.894T>G		non_coding_transcript_exon_variant	Exon 9 of 28	2		ENSP00000414386.1
RABGAP1	ENST00000426918.2	n.*662T>G		3_prime_UTR_variant	Exon 7 of 8	5		ENSP00000416327.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1098T>G (p.D366E) alteration is located in exon 8 (coding exon 7) of the RABGAP1 gene. This alteration results from a T to G substitution at nucleotide position 1098, causing the aspartic acid (D) at amino acid position 366 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.062	T
Eigen	Benign	-0.16
Eigen_PC	Benign	0.014
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.092
Sift	Benign	0.42	T
Sift4G	Benign	0.46	T
Polyphen		0.013	B
Vest4		0.37
MutPred		0.38		Gain of helix (P = 0.0199);
MVP		0.17
MPC		0.58
ClinPred		0.36	T
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.089
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.28		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-125758881;