rs1291602

Variant names:

• chr5-131430969-T-A
• rs1291602
• NM_016340.6:c.4355A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-131430969-T-A
• chr5-131430969-T-C
• chr5-131430969-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016340.6(RAPGEF6):​c.4355A>T​(p.Gln1452Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 31)
• Consequence: RAPGEF6 NM_016340.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.83
• Publications: 43 publications found

Genes affected

RAPGEF6 (HGNC:20655): (Rap guanine nucleotide exchange factor 6) Enables several functions, including GTP-dependent protein binding activity; guanyl-nucleotide exchange factor activity; and phosphatidic acid binding activity. Involved in microvillus assembly; positive regulation of GTPase activity; and protein localization to plasma membrane. Located in several cellular components, including apical plasma membrane; centrosome; and endocytic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000273217 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16448158).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016340.6. 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
	RAPGEF6	NM_016340.6	MANE Select	c.4355A>T	p.Gln1452Leu	missense	Exon 26 of 28	NP_057424.3	Q8TEU7-1
	RAPGEF6	NM_001164386.2		c.4379A>T	p.Gln1460Leu	missense	Exon 27 of 29	NP_001157858.1	Q8TEU7-4
	RAPGEF6	NM_001164387.2		c.4394A>T	p.Gln1465Leu	missense	Exon 28 of 29	NP_001157859.1	Q8TEU7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPGEF6	ENST00000509018.6	TSL:1 MANE Select	c.4355A>T	p.Gln1452Leu	missense	Exon 26 of 28	ENSP00000421684.1	Q8TEU7-1
	ENSG00000273217	ENST00000514667.1	TSL:2	c.4505A>T	p.Gln1502Leu	missense	Exon 27 of 29	ENSP00000426948.1	E9PCH4
	RAPGEF6	ENST00000296859.10	TSL:1	c.4379A>T	p.Gln1460Leu	missense	Exon 27 of 29	ENSP00000296859.6	Q8TEU7-4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 66

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.099
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.8
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.12
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.066	T
Polyphen		0.0	B
Vest4		0.31
MutPred		0.38		Gain of sheet (P = 0.039)
MVP		0.19
MPC		0.16
ClinPred		0.72	D
GERP RS		5.2
Varity_R		0.16
gMVP		0.56
Mutation Taster		=86/14	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

Other links and lift over

dbSNP: rs1291602; hg19: chr5-130766662;