rs528323494

Variant names:

• chr2-33516640-T-C
• NM_001139488.2:c.169T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-33516640-T-C
• chr2-33516640-T-G

Variant summary

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

The NM_001139488.2(RASGRP3):​c.169T>C​(p.Cys57Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000058 in 1,378,664 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C57G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000058 (0 hom.)
• Consequence: RASGRP3 NM_001139488.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.40

Genes affected

RASGRP3 (HGNC:14545): (RAS guanyl releasing protein 3) The protein encoded by this gene is a guanine nucleotide exchange factor that activates the oncogenes HRAS and RAP1A. Defects in this gene have been associated with systemic lupus erythematosus and several cancers. [provided by RefSeq, Mar 2017]

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=0.22083133).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGRP3	NM_001139488.2	c.169T>C	p.Cys57Arg	missense_variant	Exon 4 of 18	ENST00000403687.8	NP_001132960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGRP3	ENST00000403687.8	c.169T>C	p.Cys57Arg	missense_variant	Exon 4 of 18	1	NM_001139488.2	ENSP00000384192.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000580 AC: 8 AN: 1378664 Hom.: 0 Cov.: 27 AF XY: 0.00000875 AC XY: 6 AN XY: 685582

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000764

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.24	T;.;T;.;.;.;.
Eigen	Benign	-0.18
Eigen_PC	Benign	0.050
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.65	.;T;T;T;T;T;T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.22	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;.;L;.;.;.;L
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.9	N;N;N;N;N;N;N
REVEL	Benign	0.080
Sift	Benign	0.21	T;T;T;T;T;T;T
Sift4G	Benign	0.49	T;T;T;T;T;T;T
Polyphen		0.0	B;.;B;.;.;.;.
Vest4		0.49
MutPred		0.40		Gain of disorder (P = 0.0265);Gain of disorder (P = 0.0265);Gain of disorder (P = 0.0265);Gain of disorder (P = 0.0265);Gain of disorder (P = 0.0265);Gain of disorder (P = 0.0265);Gain of disorder (P = 0.0265);
MVP		0.45
MPC		0.22
ClinPred		0.44	T
GERP RS		5.8
Varity_R		0.42
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-33741707;