14-24267755-T-A

Variant names:

• chr14-24267755-T-A
• rs729421
• NM_182836.3:c.1258A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004581.5(RABGGTA):​c.1258A>T​(p.Thr420Ser) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RABGGTA NM_004581.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• Publications: 46 publications found

Genes affected

RABGGTA (HGNC:9795): (Rab geranylgeranyltransferase subunit alpha) Predicted to enable small GTPase binding activity. Predicted to contribute to Rab geranylgeranyltransferase activity. Predicted to be involved in protein geranylgeranylation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000288044 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044955283).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004581.5. 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
	RABGGTA	NM_182836.3	MANE Select	c.1258A>T	p.Thr420Ser	missense	Exon 14 of 17	NP_878256.1
	RABGGTA	NM_004581.5		c.1258A>T	p.Thr420Ser	missense	Exon 13 of 16	NP_004572.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABGGTA	ENST00000216840.11	TSL:1 MANE Select	c.1258A>T	p.Thr420Ser	missense	Exon 14 of 17	ENSP00000216840.6
	RABGGTA	ENST00000399409.7	TSL:1	c.1258A>T	p.Thr420Ser	missense	Exon 13 of 16	ENSP00000382341.3
	RABGGTA	ENST00000876595.1		c.1258A>T	p.Thr420Ser	missense	Exon 14 of 17	ENSP00000546654.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Benign	0.86
DEOGEN2	Benign	0.081	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.39	N
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N
PhyloP100		2.0
PrimateAI	Benign	0.42	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.022
Sift	Benign	0.46	T
Sift4G	Benign	0.78	T
Polyphen		0.0	B
Vest4		0.070
MutPred		0.30		Gain of catalytic residue at M417 (P = 0.0013)
MVP		0.38
MPC		0.11
ClinPred		0.16	T
GERP RS		3.7
PromoterAI		-0.013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.032
gMVP		0.19
Mutation Taster		=98/2	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: rs729421; hg19: chr14-24736961;