rs1037528236

Variant names:

• chr19-2717236-C-A
• rs1037528236
• NM_145173.4:c.571G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-2717236-C-A
• chr19-2717236-C-T

Variant summary

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

The NM_145173.4(DIRAS1):​c.571G>T​(p.Val191Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DIRAS1 NM_145173.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186

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]

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=0.06948459).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIRAS1	NM_145173.4	c.571G>T	p.Val191Phe	missense_variant	Exon 2 of 2	ENST00000323469.5	NP_660156.1
DIRAS1	XM_047438274.1	c.673G>T	p.Val225Phe	missense_variant	Exon 3 of 3		XP_047294230.1
DIRAS1	XM_047438275.1	c.673G>T	p.Val225Phe	missense_variant	Exon 3 of 3		XP_047294231.1
DIRAS1	XM_047438276.1	c.673G>T	p.Val225Phe	missense_variant	Exon 3 of 3		XP_047294232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIRAS1	ENST00000323469.5	c.571G>T	p.Val191Phe	missense_variant	Exon 2 of 2	1	NM_145173.4	ENSP00000325836.3
DIRAS1	ENST00000585334.1	c.571G>T	p.Val191Phe	missense_variant	Exon 1 of 1	6		ENSP00000468417.1
DIRAS1	ENST00000588128.1	c.*163G>T		downstream_gene_variant		4		ENSP00000466733.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000405 AC: 1 AN: 247090 Hom.: 0 AF XY: 0.00000745 AC XY: 1 AN XY: 134228

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000329

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1445162 Hom.: 0 Cov.: 33 AF XY: 0.00000140 AC XY: 1 AN XY: 715752

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.048	T;T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.91	.;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.069	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.74	N;.
REVEL	Benign	0.10
Sift	Benign	0.11	T;.
Sift4G	Benign	0.083	T;T
Polyphen		0.0	B;B
Vest4		0.16
MutPred		0.28		Gain of sheet (P = 0.0061);Gain of sheet (P = 0.0061);
MVP		0.32
MPC		1.4
ClinPred		0.065	T
GERP RS		-2.1
Varity_R		0.093
gMVP		0.52

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: rs1037528236; hg19: chr19-2717234;