18-9859266-A-G

Position:

• chr18-9859266-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000578921.6(RAB31):​c.529A>G​(p.Asn177Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,656 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RAB31 ENST00000578921.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.22

Genes affected

RAB31 (HGNC:9771): (RAB31, member RAS oncogene family) Enables GDP binding activity and GTP binding activity. Involved in several processes, including Golgi to plasma membrane protein transport; cellular response to insulin stimulus; and receptor internalization. Located in early endosome; phagocytic vesicle; and trans-Golgi network membrane. Biomarker of severe acute respiratory syndrome. [provided by Alliance of Genome Resources, Apr 2022]

RAB31 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1707702).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB31	NM_006868.4	c.529A>G	p.Asn177Asp	missense_variant	7/7	ENST00000578921.6	NP_006859.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB31	ENST00000578921.6	c.529A>G	p.Asn177Asp	missense_variant	7/7	1	NM_006868.4	ENSP00000461945.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461656 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727106

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2023

The c.529A>G (p.N177D) alteration is located in exon 7 (coding exon 7) of the RAB31 gene. This alteration results from a A to G substitution at nucleotide position 529, causing the asparagine (N) at amino acid position 177 to be replaced by an aspartic acid (D). 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
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Benign	-0.16
Eigen_PC	Benign	0.065
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	0.73	D;D
PrimateAI	Uncertain	0.59	T
Sift4G	Benign	0.64	T
Vest4		0.29
MVP		0.78
MPC		0.54
ClinPred		0.69	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs746508290; hg19: chr18-9859263;