14-24267710-C-G

Variant names:

• chr14-24267710-C-G
• rs370570899
• NM_182836.3:c.1303G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182836.3(RABGGTA):​c.1303G>C​(p.Val435Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,612,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V435M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RABGGTA NM_182836.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08407855).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182836.3. 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.1303G>C	p.Val435Leu	missense	Exon 14 of 17	NP_878256.1	Q92696
	RABGGTA	NM_004581.5		c.1303G>C	p.Val435Leu	missense	Exon 13 of 16	NP_004572.3	Q92696

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABGGTA	ENST00000216840.11	TSL:1 MANE Select	c.1303G>C	p.Val435Leu	missense	Exon 14 of 17	ENSP00000216840.6	Q92696
	RABGGTA	ENST00000399409.7	TSL:1	c.1303G>C	p.Val435Leu	missense	Exon 13 of 16	ENSP00000382341.3	Q92696
	RABGGTA	ENST00000876595.1		c.1303G>C	p.Val435Leu	missense	Exon 14 of 17	ENSP00000546654.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459708 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726142

African (AFR) AF: 0.00 AC: 0 AN: 33416

American (AMR) AF: 0.00 AC: 0 AN: 44706

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4178

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111816

Other (OTH) AF: 0.00 AC: 0 AN: 60198

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152294 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74456

African (AFR) AF: 0.00 AC: 0 AN: 41550

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Benign	0.89
DEOGEN2	Benign	0.064	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.84	D
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.52	N
PhyloP100		1.7
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.76	N
REVEL	Benign	0.046
Sift	Benign	0.30	T
Sift4G	Benign	0.87	T
Polyphen		0.0	B
Vest4		0.22
MutPred		0.49		Gain of catalytic residue at N433 (P = 0.0126)
MVP		0.30
MPC		0.12
ClinPred		0.28	T
GERP RS		2.1
PromoterAI		0.0083	Neutral
Varity_R		0.028
gMVP		0.27
Mutation Taster		=88/12	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: rs370570899; hg19: chr14-24736916;