RANGAP1 p.Glu364Asp

Variant names:

• chr22-41254476-C-A
• NM_002883.4:c.1092G>T
• RANGAP1 p.Glu364Asp

Your query was ambiguous. Multiple possible variants found:

• chr22-41254476-C-A
• chr22-41254476-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002883.4(RANGAP1):​c.1092G>T​(p.Glu364Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RANGAP1 NM_002883.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.643
• Publications: 0 publications found

Genes affected

RANGAP1 (HGNC:9854): (Ran GTPase activating protein 1) This gene encodes a protein that associates with the nuclear pore complex and participates in the regulation of nuclear transport. The encoded protein interacts with Ras-related nuclear protein 1 (RAN) and regulates guanosine triphosphate (GTP)-binding and exchange. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039599508).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002883.4. 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
	RANGAP1	NM_002883.4	MANE Select	c.1092G>T	p.Glu364Asp	missense	Exon 11 of 16	NP_002874.1	P46060
	RANGAP1	NM_001278651.2		c.1092G>T	p.Glu364Asp	missense	Exon 12 of 17	NP_001265580.1	P46060
	RANGAP1	NM_001317930.2		c.1092G>T	p.Glu364Asp	missense	Exon 11 of 16	NP_001304859.1	P46060

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RANGAP1	ENST00000356244.8	TSL:1 MANE Select	c.1092G>T	p.Glu364Asp	missense	Exon 11 of 16	ENSP00000348577.3	P46060
	RANGAP1	ENST00000405486.5	TSL:1	c.1092G>T	p.Glu364Asp	missense	Exon 12 of 17	ENSP00000385866.1	P46060
	RANGAP1	ENST00000455915.6	TSL:1	c.1092G>T	p.Glu364Asp	missense	Exon 10 of 15	ENSP00000401470.2	P46060

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.82
DANN	Benign	0.072
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.085	N
PhyloP100		0.64
PrimateAI	Benign	0.42	T
PROVEAN	Benign	1.0	N
REVEL	Benign	0.028
Sift	Benign	1.0	T
Sift4G	Benign	0.68	T
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.9
Varity_R		0.020
gMVP		0.026
Mutation Taster		=89/11	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-41650480;