Variant 2-131363309-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001077637.3(RAB6D):c.412A>G(p.Ile138Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000657 in 1,613,834 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 25)

Exomes 𝑓: 0.000043 ( 1 hom. )

Consequence

RAB6D
NM_001077637.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.47

Variant links:

Genes affected

RAB6D (HGNC:30272): (RAB6D, member RAS oncogene family) Predicted to enable GTPase activity. Predicted to be involved in Golgi vesicle transport; intracellular protein transport; and retrograde transport, endosome to Golgi. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

RAB6D links:

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ACMG classification

Classification made for transcript

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=0.08887428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB6D	NM_001077637.3 linkuse as main transcript	c.412A>G	p.Ile138Val	missense_variant	1/1	ENST00000623617.3	NP_001071105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB6D	ENST00000623617.3 linkuse as main transcript	c.412A>G	p.Ile138Val	missense_variant	1/1		NM_001077637.3	ENSP00000490038	P1

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000604

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000756

AC:

AN:

251462

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000431

AC:

AN:

1461722

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000283

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.000604

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000288

Hom.:

ExAC

AF:

0.000148

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2021

The c.412A>G (p.I138V) alteration is located in exon 1 (coding exon 1) of the WTH3DI gene. This alteration results from a A to G substitution at nucleotide position 412, causing the isoleucine (I) at amino acid position 138 to be replaced by a valine (V). 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

AlphaMissense

Benign

0.067

BayesDel_noAF

Benign

-0.67

CADD

Benign

9.2

DANN

Benign

0.71

DEOGEN2

Benign

0.17

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.61

MetaRNN

Benign

0.089

PrimateAI

Uncertain

0.53

Polyphen

0.0

GERP RS

1.1

Varity_R

0.022

gMVP

0.11

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over