rs770249841

Variant names:

• chr22-41249749-C-A
• NM_002883.4:c.1552G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-41249749-C-A
• chr22-41249749-C-T

Variant summary

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

The NM_002883.4(RANGAP1):​c.1552G>T​(p.Val518Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,542 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 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. V518M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RANGAP1 NM_002883.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RANGAP1	NM_002883.4	c.1552G>T	p.Val518Leu	missense_variant	Exon 14 of 16	ENST00000356244.8	NP_002874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RANGAP1	ENST00000356244.8	c.1552G>T	p.Val518Leu	missense_variant	Exon 14 of 16	1	NM_002883.4	ENSP00000348577.3
RANGAP1	ENST00000405486.5	c.1552G>T	p.Val518Leu	missense_variant	Exon 15 of 17	1		ENSP00000385866.1
RANGAP1	ENST00000455915.6	c.1552G>T	p.Val518Leu	missense_variant	Exon 13 of 15	1		ENSP00000401470.2
RANGAP1	ENST00000705116.1	c.1552G>T	p.Val518Leu	missense_variant	Exon 14 of 16			ENSP00000516069.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461542 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727112

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.45	T;T;T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.88	.;.;D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.45	T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.4	M;M;M
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.099
Sift	Uncertain	0.0090	D;D;D
Sift4G	Uncertain	0.015	D;D;D
Polyphen		0.19	B;B;B
Vest4		0.25
MutPred		0.78		Loss of helix (P = 0.2662);Loss of helix (P = 0.2662);Loss of helix (P = 0.2662);
MVP		0.53
MPC		0.35
ClinPred		0.80	D
GERP RS		-0.10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.46
gMVP		0.35

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-41645753;