1-205771540-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003929.3(RAB29):c.310C>G(p.Gln104Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0146 in 1,614,136 control chromosomes in the GnomAD database, including 256 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0098 (13 hom., cov: 32)
  • Exomes 𝑓: 0.015 (243 hom.)
• Consequence: RAB29 NM_003929.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.02

Genes affected

RAB29 (HGNC:9789): (RAB29, member RAS oncogene family) Enables several functions, including dynein complex binding activity; guanyl ribonucleotide binding activity; and kinesin binding activity. Involved in several processes, including positive regulation of T cell receptor signaling pathway; positive regulation of receptor recycling; and toxin transport. Located in several cellular components, including Golgi apparatus; endosome; and vacuole. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007671267).
• BP6: Variant 1-205771540-G-C is Benign according to our data. Variant chr1-205771540-G-C is described in ClinVar as [Benign]. Clinvar id is 3037484.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-205771540-G-C is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00979 (1491/152288) while in subpopulation SAS AF= 0.0249 (120/4822). AF 95% confidence interval is 0.0213. There are 13 homozygotes in gnomad4. There are 748 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB29	NM_003929.3	c.310C>G	p.Gln104Glu	missense_variant	4/6	ENST00000367139.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB29	ENST00000367139.8	c.310C>G	p.Gln104Glu	missense_variant	4/6	1	NM_003929.3	P1

Frequencies

GnomAD3 genomes AF: 0.00982 AC: 1494 AN: 152170 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.00232

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.00635

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0249

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0143

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.0125 AC: 3142 AN: 251490 Hom.: 39 AF XY: 0.0140 AC XY: 1897 AN XY: 135920

Gnomad AFR exome AF: 0.00209

Gnomad AMR exome AF: 0.00416

Gnomad ASJ exome AF: 0.0121

Gnomad EAS exome AF: 0.000217

Gnomad SAS exome AF: 0.0292

Gnomad FIN exome AF: 0.0134

Gnomad NFE exome AF: 0.0139

Gnomad OTH exome AF: 0.0114

GnomAD4 exome AF: 0.0151 AC: 22117 AN: 1461848 Hom.: 243 Cov.: 32 AF XY: 0.0157 AC XY: 11429 AN XY: 727228

Gnomad4 AFR exome AF: 0.00218

Gnomad4 AMR exome AF: 0.00454

Gnomad4 ASJ exome AF: 0.0108

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.0303

Gnomad4 FIN exome AF: 0.0125

Gnomad4 NFE exome AF: 0.0155

Gnomad4 OTH exome AF: 0.0148

GnomAD4 genome AF: 0.00979 AC: 1491 AN: 152288 Hom.: 13 Cov.: 32 AF XY: 0.0100 AC XY: 748 AN XY: 74452

Gnomad4 AFR AF: 0.00231

Gnomad4 AMR AF: 0.00627

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0249

Gnomad4 FIN AF: 0.0124

Gnomad4 NFE AF: 0.0143

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.0126 Hom.: 11

Bravo AF: 0.00868

TwinsUK AF: 0.0138 AC: 51

ALSPAC AF: 0.0179 AC: 69

ESP6500AA AF: 0.00386 AC: 17

ESP6500EA AF: 0.0143 AC: 123

ExAC AF: 0.0128 AC: 1559

Asia WGS AF: 0.0130 AC: 47 AN: 3478

EpiCase AF: 0.0157

EpiControl AF: 0.0152

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

RAB29-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.28
Cadd	Benign	21
Dann	Benign	0.45
DEOGEN2	Benign	0.15	T;T;.;.;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.049
FATHMM_MKL	Uncertain	0.94	D
MetaRNN	Benign	0.0077	T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	-0.45	N;N;.;.;N
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.15	N;N;N;N;N
REVEL	Benign	0.26
Sift	Benign	0.95	T;T;T;T;T
Sift4G	Benign	0.96	T;T;T;T;T
Polyphen		0.0010	B;B;.;.;B
Vest4		0.098
MPC		0.50
ClinPred		0.038	T
GERP RS		5.3
Varity_R		0.22
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs41302139; hg19: chr1-205740668; COSMIC: COSV99030272; COSMIC: COSV99030272;