rs528323494

Variant names:

• chr2-33516640-T-G
• rs528323494
• NM_001139488.2:c.169T>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001139488.2(RASGRP3):​c.169T>G​(p.Cys57Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,531,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: RASGRP3 NM_001139488.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10316014).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001139488.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGRP3	NM_001139488.2	MANE Select	c.169T>G	p.Cys57Gly	missense	Exon 4 of 18	NP_001132960.1	Q8IV61-1
	RASGRP3	NM_001349975.2		c.169T>G	p.Cys57Gly	missense	Exon 6 of 20	NP_001336904.1	Q8IV61-1
	RASGRP3	NM_001349976.2		c.169T>G	p.Cys57Gly	missense	Exon 4 of 18	NP_001336905.1	Q8IV61-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGRP3	ENST00000403687.8	TSL:1 MANE Select	c.169T>G	p.Cys57Gly	missense	Exon 4 of 18	ENSP00000384192.3	Q8IV61-1
	RASGRP3	ENST00000402538.8	TSL:1	c.169T>G	p.Cys57Gly	missense	Exon 5 of 19	ENSP00000385886.3	Q8IV61-1
	RASGRP3	ENST00000407811.5	TSL:1	c.169T>G	p.Cys57Gly	missense	Exon 3 of 17	ENSP00000383917.1	Q8IV61-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152246 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000300 AC: 6 AN: 199984 AF XY: 0.0000375

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000403

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000123 AC: 17 AN: 1378666 Hom.: 0 Cov.: 27 AF XY: 0.0000204 AC XY: 14 AN XY: 685582

African (AFR) AF: 0.00 AC: 0 AN: 31826

American (AMR) AF: 0.00 AC: 0 AN: 40046

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25276

East Asian (EAS) AF: 0.000414 AC: 16 AN: 38612

South Asian (SAS) AF: 0.00 AC: 0 AN: 80556

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51750

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5598

European-Non Finnish (NFE) AF: 9.55e-7 AC: 1 AN: 1047326

Other (OTH) AF: 0.00 AC: 0 AN: 57676

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152364 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74502

African (AFR) AF: 0.00 AC: 0 AN: 41590

American (AMR) AF: 0.00 AC: 0 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000167 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Benign	0.88
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.076
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.4
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.087
Sift	Benign	0.17	T
Sift4G	Benign	0.36	T
Polyphen		0.0020	B
Vest4		0.48
MutPred		0.41		Gain of disorder (P = 0.0313)
MVP		0.50
MPC		0.14
ClinPred		0.077	T
GERP RS		5.8
Varity_R		0.16
gMVP		0.18
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs528323494; hg19: chr2-33741707;