NM_182836.3:c.1312A>T

Variant names:

• chr14-24267701-T-A
• rs201017775
• NM_182836.3:c.1312A>T

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.1312A>T​(p.Met438Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000744 in 1,611,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: RABGGTA NM_182836.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.37
• 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=0.18006861).

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.1312A>T	p.Met438Leu	missense	Exon 14 of 17	NP_878256.1	Q92696
	RABGGTA	NM_004581.5		c.1312A>T	p.Met438Leu	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.1312A>T	p.Met438Leu	missense	Exon 14 of 17	ENSP00000216840.6	Q92696
	RABGGTA	ENST00000399409.7	TSL:1	c.1312A>T	p.Met438Leu	missense	Exon 13 of 16	ENSP00000382341.3	Q92696
	RABGGTA	ENST00000876595.1		c.1312A>T	p.Met438Leu	missense	Exon 14 of 17	ENSP00000546654.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152128 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000201 AC: 5 AN: 248980 AF XY: 0.0000148

Gnomad AFR exome AF: 0.000323

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000480 AC: 7 AN: 1459682 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726128

African (AFR) AF: 0.000150 AC: 5 AN: 33416

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86164

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4168

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111814

Other (OTH) AF: 0.0000166 AC: 1 AN: 60194

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152246 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74446

African (AFR) AF: 0.000120 AC: 5 AN: 41538

American (AMR) AF: 0.00 AC: 0 AN: 15294

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000491

ESP6500AA AF: 0.000916 AC: 4

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000412 AC: 5

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	Benign	0.31
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.036
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	M
PhyloP100		6.4
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.11
Sift	Benign	0.33	T
Sift4G	Benign	0.76	T
Polyphen		0.25	B
Vest4		0.65
MutPred		0.49		Gain of catalytic residue at N433 (P = 0.0099)
MVP		0.31
MPC		0.28
ClinPred		0.31	T
GERP RS		5.4
PromoterAI		-0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.42
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: rs201017775; hg19: chr14-24736907;