Variant 19-2717776-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_145173.4(DIRAS1):c.31G>A(p.Val11Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,449,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DIRAS1
NM_145173.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.65

Variant links:

Genes affected

DIRAS1 (HGNC:19127): (DIRAS family GTPase 1) DIRAS1 belongs to a distinct branch of the functionally diverse Ras (see HRAS; MIM 190020) superfamily of monomeric GTPases.[supplied by OMIM, Apr 2004]

DIRAS1 links:

ENSG00000267001 (HGNC:):

ENSG00000267001 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.849

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIRAS1	NM_145173.4 linkuse as main transcript	c.31G>A	p.Val11Met	missense_variant	2/2	ENST00000323469.5	NP_660156.1	O95057
DIRAS1	XM_047438274.1 linkuse as main transcript	c.133G>A	p.Val45Met	missense_variant	3/3		XP_047294230.1
DIRAS1	XM_047438275.1 linkuse as main transcript	c.133G>A	p.Val45Met	missense_variant	3/3		XP_047294231.1
DIRAS1	XM_047438276.1 linkuse as main transcript	c.133G>A	p.Val45Met	missense_variant	3/3		XP_047294232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DIRAS1	ENST00000323469.5 linkuse as main transcript	c.31G>A	p.Val11Met	missense_variant	2/2	1	NM_145173.4	ENSP00000325836.3	O95057
ENSG00000267001	ENST00000586572.1 linkuse as main transcript	c.310G>A	p.Val104Met	missense_variant	3/3	4		ENSP00000467958.1	K7EQS6
DIRAS1	ENST00000585334.1 linkuse as main transcript	c.31G>A	p.Val11Met	missense_variant	1/1	6		ENSP00000468417.1	O95057
DIRAS1	ENST00000588128.1 linkuse as main transcript	c.31G>A	p.Val11Met	missense_variant	3/3	4		ENSP00000466733.1	K7EN06

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000832

AC:

AN:

240344

Hom.:

AF XY:

0.00000762

AC XY:

AN XY:

131158

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000201

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000138

AC:

AN:

1449232

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721370

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 16, 2024

The c.31G>A (p.V11M) alteration is located in exon 2 (coding exon 1) of the DIRAS1 gene. This alteration results from a G to A substitution at nucleotide position 31, causing the valine (V) at amino acid position 11 to be replaced by a methionine (M). 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

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.46

T;T;T;.

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.98

.;D;D;T

M_CAP

Uncertain

0.22

MetaRNN

Pathogenic

0.85

D;D;D;D

MetaSVM

Uncertain

0.58

MutationAssessor

Uncertain

2.7

M;M;.;.

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-2.1

N;.;.;.

REVEL

Pathogenic

0.85

Sift

Uncertain

0.0010

D;.;.;.

Sift4G

Pathogenic

0.0010

D;D;D;.

Polyphen

1.0

D;D;.;.

Vest4

0.79

MutPred

0.72

Gain of disorder (P = 0.1225);Gain of disorder (P = 0.1225);Gain of disorder (P = 0.1225);.;

MVP

0.85

MPC

2.3

ClinPred

0.93

GERP RS

3.9

Varity_R

0.73

gMVP

0.89

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

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